midterm Flashcards

Question

Zygote to Morula

Answer 1

- zygote proliferates (mitotic divisions) without differentiating - generates a solid mass of cells (=morula) that stick together via 'cell adhesion molecules' - morula moves down the uterine tube into the uterus proper.

Answer 2

- Morula pumps fluid into its center to form a central cavity - structure now known as the 'blastocyst' - significant differentiation

Answer 3

form embryo proper | -during implatation; splits into two layers of cells and differentiate into the epiblast and the hypoblast

Answer 4

help to form the fetal portion of the placenta the cells are "extraembryonic" -during implantation; split into two layers which differentiate into the inner, fully cellularized 'cytotropholasts' that proliferate, and the outer fused/multinucleate 'syncytiotrophoblasts' (= syncytium) - surrounded the entire blastocyst as it enters the uterine wall

Answer 5

- send finger-like projections deep into the uterine wall that release proteolytic/digestive enzymes that facilitate the implantation of the embryo - release human chorionic gonadotrophin (hCG) to maintain the corpus luteum in the ovary

Answer 6

- keeps producing estrogen and progesterone | - maintain the uterine wall (ie. prevents menstruation that would lead to the loss of the implanted early embryo)

Answer 7

- spaces that form within the core of syncytiotrophoblast fingers - in the placenta; - > they expand and fuse to form the large 'intervillous spaces' that are filled with maternal blood

Answer 8

- consists of totipotent embryonic stem cells and amnionic cells - during the formation of the extraembryonic membrane and placenta; - > splits and the 'amniotic cavity' forms within it - > the layer of epiblast cells adjacent to the cytotrophoblasts become 'amnioblasts' - > gives rise to the extraembryonic mesoderm

Answer 9

- generates the cells of the Heuser's membrane which delineate the margin of the yolk sac.

Answer 10

- form the "extraembryonic" amniotic membrane that line the amniotic cavity

Answer 11

anything that will not form the embryonic tissues that ultimately give rise fetus proper

Answer 12

- contributes to all of the major extraembryonic membranes that surround the embryo proper (eg. it contributes to the linings of the chorionic amniotic and yolk sac cavities) and the placenta. - gives rise the extaembyronic blood vessels that exchange gases, nutrients and waste with the maternal blood in the trophoblastic lacuna. - migrate out from the epiblast and line the Heuser's membrane and the cytotrophoblast and surround the embryo proper as well as the yolk sac.

Answer 13

-Maternal/Uterine component (='decidua basalis') -Embryonic/Fetal component (='chorionic villi') syncytiotrophoblasts, cytoblasts and the cells that line the extraembryonic/fetal blood vessels derived from the extraembryonic membrane

Answer 14

- mostly maternal arteries and veins which supply and drain the 'trophoblastic lacuna'

Answer 15

- single chorionic villus is a finger of extraembryonic tissues - made up of syncytiotrophoblasts and cytotrophoblasts that surround a core of extraembryonic mesoderm to exchange gases, nutrients and waste in the trophoblastic lacuna

Answer 16

syncytiotrophoblasts, cytoblasts and the cells that line the extraembryonic/fetal blood vessels derived from the extraembryonic membrane

Answer 17

- formed from epiblasts which splits and fluid starts to accumulate in the cavity that forms within it. Embryogenesis happens in the amnionic cavity. - provides a large fluid filled cavity to protect the embryo and fetus; helps eliminate waste.

Answer 18

- formed from hypoblasts that migrate along Heuser's membrane which first delineates the fluid-filled yolk sac. - part breaks off later on and is reabsorbed. - a transient structure that produces blood cells until the liver forms; germ cells form in the yolk sac and migrate to the gonads

Answer 19

- forms between (What layer??) two layers of mesoderm as fluid fills in gaps. - it becomes a potential space, and amnion replaces this space as it expands through the embryonic period and, especially the later fetal period.

Answer 20

A small number of cells sluff off into the amniotic fluid | - the cells can be removed from the fluid and their chromosomes/genes can be analyzed

Answer 21

Gastrulation is the conversion of the BILAMINAR (epiblast and hypoblast) embryo into three germ layers (ectoderm, mesoderm, endoderm).

Answer 22

- Formed from the epiblast - starts at the caudal/tail end of the embryo - as the epibalst cells divide/proliferate the lateral edges of the streak they start to push upward and the cells at the centre ingress - sets the axes of the embryo - the anterior portion is called the primitive node which moves toward what will form the cranial/head end of the embryo

Answer 23

- the formation of the primitive streak, the primitive node

Answer 24

- the cells that ingress into the primitive streak start to express novel sets of genes (differentiate). - causes the cells to cease being 'epithelial' and become single and migratory = 'mesenchyme'

Answer 25

- first wave of mesenchymal cells push down into, and replace, almost all the cells of the hypoblast and become the endoderm

Answer 26

-many of the innermost lining tissues of the body (ie. much of the GI, Respiratory and Urinary tracts).

Answer 27

- 2nd wave of mesenchymal cells push between the epiblast and hypoblast to form the mesoderm - early on different regions regulate the induction of tissues and structures

Answer 28

-most of the 'packing' tissues of the body (ie. muscle, bone, cartilage, connective tissue, blood, fetal/post-natal blood vessels)

Answer 29

- the notochord formed from the mesoderm induces the formation of the neural tube - the precordal mesoderm moves cranially and induces the formation of the portion of the neural tube that forms the brain - Formation of the brain requires the expression of the transcription factor Lim1, with out Lim1 there is no head and brain formation

Answer 30

- segmented "somites" that generate skeletal muscle, cartilage, and tendons as well as much of the dermis

Answer 31

- cells that don't enter the primitive streak and remain in the top layer of the developing embryo form the 'ectoderm' which gives rise to most of the outer covering tissue of the body (ie. skin) and the nervous tissue (by 'induction'; see below).

Answer 32

- most of the outer covering tissue of the body (ie. skin) and the nervous tissue (by 'induction')

Answer 33

- the last mesenchymal cells to move through the primitive streak aggregate to form a solid cord of mesodermal cells in the midline = 'notocord' - located just below the ectoderm that will form the spinal cord.

Answer 34

Formation of the neural tube, done by the process of "induction"

Answer 35

- process whereby one cell or group of cells influences the developmental fate of another. e. g. the Notochord and prechordal mesoderm induce the overlying ectoderm to form nervous tissue.

Answer 36

- notochord releases short range-acting molecules that induce formation of the central nervous system (CNS) by signaling the ectoderm directly above it to thicken

Answer 37

- neuroectodermal cells of the neural plate change shape such that it folds in upon itself to form the ‘neural groove’. - These cells change their cell-cell adhesion molecules to a neural form (eg N-cadherin) which is different from those expressed in remainder of the ectoderm (eg. E-Cadherin). - allows the tissues to separate from each other.

Answer 38

- A small number of the N-cadherin producing neuroectodermal cells pinch off from the developing neural tube and move laterally to form the neural crest

Answer 39

- the neural plate buckles inward, the mesoderm alongside the spinal cord portion of the neural tube differentiates to form the three mesodermal regions: 1) paraxial (somites, forming in a cranial to caudal fashion) 2) intermediate 3) lateral plate

Answer 40

- segmented blocks of mesoderm on each side of the midline give rise to most of the skeleton and all the voluntary musculature.

Answer 41

- neural tube forms specialized regions to produce different cell types ex dorsal plate for sensory information and ventral plate for motor information - the developing spinal cord portion of the tube 'positional cues' come initially from two regions: 1) Notochord 2) Dorsal Ectoderm Cells - the combination of chemical gradients provide ventral/dorsal spatial information across the neural tube which induces different combinations of transcription factors to be expressed in different spatial domains that cause differentiation in those domains

Answer 42

- Sonichedgehog (Shh) which diffuses and decreases in concentration as it moves dorsally

Answer 43

binds DNA at specific sequences to turn on/off specific genes in clusters of cells that act as 'progenitors' which have stem like characteristics.

Answer 44

- Bone Morphogenetic Protein (BMP) which diffuses and decreases in concentration as it moves ventrally

Answer 45

- outer polar heads - dark on TEM - middle hydrophobic tails - light on TEM - inner polar heads - dark on TEM

Answer 46

- Integral membrane proteins spans the phospholipid bilayer - Covalently-linked to a fatty acid tail (e.g. palmitoylation) that inserts in membrane - Covalently-linked to a specialized phospholipid (eg. glycophosphatidylinositol-GPI) that inserts in the membrane - Peripheral proteins that associate with an integral membrane protein (i.e. in close proximity to, but not inserted into the phospholipid bilayer)

Answer 47

Adenlyate cyclase

Answer 48

PLC which turns PtdIns4,5P2 into the messenger

Answer 49

InsP3 and diacylglycerol

Answer 50

- site of biogenesis of other organelles - RER Functions in protein synthesis and post-translational modification (glycosylation, adding disulfide bonds and protein folding) and SER is important in lipid synthesis and intracellular calcium storage. - Also site of many detoxification enzymes, particularly in liver hepatocytes.

Answer 51

signal sequence' = N-terminal portion of growing peptide, which binds to the.... • 'signal recognition particle' in the cytoplasm, which binds to the... • 'signal recognition particle (SRP) receptor' on the ER membrane which contributes to the formation of a channel that threads growing peptide into the ER lumen where the.... • 'signal peptidase' removes the signal sequence from the polypeptide in the ER lumen and... • 'post-translational modifications' occur including protein folding, disulphide bond formation between strands of the protein, and glycosylation of the protein. These steps occur in the ER lumen to generate a 'completed protein' for packaging and eventual export from the ER to other cellular sites or secretion from the cell

Answer 52

i) ER-associated degradation (ERAD) of the misfolded protein; specifically, it is removed from the ER and destroyed in lysosomes or the proteosome (see 05Lect Cell II) ii) An upregulation of the ER machinery that facilitates protein folding (induces the production of protein chaperones and lipid synthesis that associate with and help proteins fold) iii) 'Apoptosis'; this is the last resort whereby, if large amounts of misfolded protein cannot be destroyed or re-folded, the cell initiates a program that ultimately leads to cell death (also known as 'programmed cell death')

Answer 53

•mutations in the Cystic Fibrosis Transmembrane Regulator gene, which codes for an integral transmembrane protein that is a chloride channel, prevent proper protein folding and initiate a UPR which reduces transport of the CFTR channel from ER to the plasma membrane and increases its destruction by ERAD. * Loss of CFTR causes Cystic Fibrosis* - treatment: - > gene therapy (delivering the wild-type gene via viruses) - > pharmacologically suppress the UPR to increase delivery of the protein b/c some are still functional even with the mutations

Answer 54

- 'cis' face that receives vesicles from the ER and a 'trans' face that releases mature vesicles to go to various locations in the cell

Answer 55

- cargo moves through the Golgi via small, spherical vesicles that bud off an individual cisterna and move to the next cisterna in the stack. - In this model the Golgi itself would be static while the cargo is dynamically moved through it in vesicles.

Answer 56

- the cisternae themselves move through the stack carrying cargo along with them - in this model the small vesicles bud off and travel back down the stack (i.e. back towards the cis face) to recycle the Golgi enzymes so that they can work on the next wave of cargo that arrives from the ER.

Answer 57

- Phagocytosis, Pinocytosis, Receptor-mediated | - counter act exocytosis

Answer 58

1. Lysosomal enzyme (= cargo molecule), which needs to be trafficked/sorted to the lysosome, is phosphorylated on mannose to generate 'mannose-6-phosphate' (M6P) in the cis-Golgi. 2. M6P binds to the 'M6P Receptor in the trans-Golgi which recruits the coat protein clathrin. 3. A vesicle containing the enzyme-receptor complex buds from the trans-Golgi. 4. The vesicle uncoats and is then targetted to and fuses with the late endosome. 5/6. The acidic pH of the late endosome releases of the lysosomal enzyme from the M6P receptor. 7/8. The free M6P receptor is then recycled back to trans-Golgi, while the lysosomal enzyme is dephosphorylated and traffics to the lysosome where it is now active (i.e. due to the low pH and dephosphorylation).

Answer 59

1.The secreted lysosomal enzyme binds M6P receptor on the plasma membrane. 2.The enzyme-receptor complex recruits clathrin and an endocytic vesicle forms that buds into the cytoplasm 3/4. The vesicle uncoats and fuses with an early endosome, which then fuses with a late endosome. 5. The acidic pH of the late endosome releases the lysosomal enzyme from the M6P receptor and dephosphorylates the enzyme itself. 6/7/8. The M6P receptor then recycles back to either trans-Golgi or the plasma membrane; the dephosporylated, active lysosomal enzyme is trafficked to the lysosome.

Answer 60

Doesn't have the Hexosaminidase A (Hex-A) enzyme, which acts to break down specific types of lipid (eg. ganglioside GM2). Therefore, these lipids accumulate abnormally in lysosomes to toxic levels, especially in nerve cells in the brain.

Answer 61

- Deposits of cholesterol in skin. - Occurs in patients with a deficiency in Low Density Lipoprotein receptors (LDL normally carries the lipid cholesterol in blood). This most often occurs because the LDL receptor is not trafficked to/recycled from the plasmamembrane correctly. - Because of this deficiency, cells can't take in LDL and can't catabolize cholesterol, resulting in high levels of circulating cholesterol in the blood (hypercholesterolemia) and lipid/cholesterol deposits/swellings in the skin = xanthomas.

Answer 62

-Lipids can be trafficked either: 1) In vesicles (ie. within the membranes of vesicles that directly fuse, as described above, with other vesicles, with other membrane-bound organelles, or with the plasma membrane). 2) In a non-vesicular manner hidden within lipid transfer proteins (LTP's) that are soluble in aqueous solution, most often across short cytoplasmic gaps between membranes that are in close contact with each other.

Answer 63

- Glycerolipids: has a glycerol backbone, and a hydrophilic choline as well as two hydrophilic fatty acids - Sphingolipids: has a sphingosine instead of a glycerol backbone; some still have a choline attached like glycerolipids, while others have a sugar attached; as well as one fatty acid - Sterols: e.g. cholesterol

Answer 64

1. LTP binds to receptors on donor membrane and loads cholesterol into the barrel of the LTP. 2. LTP dissociates from the donor membrane and diffuses to the acceptor membrane. 4. LTP binds the acceptor membrane via receptor, into and unloads the cholesterol into the acceptor membrane. 5. LTP dissociates from the acceptor membrane so that it can used to transport another lipid

Answer 65

- lipids are transported from one membrane to another across a cytoplasmic gap at defined sites where the membranes are very close together (10-50nm), the gaps are know as ER Junctions (ERJ) - transported inside the aqueous soluble LTP's which have hydrophobic pocket/barrel to hide the lipid from the cytoplasm - there are many families of LTP's which carry specific lipids to and from various structures in the cell, either for transport or for lipid synthesis/modification

Answer 66

- for non-vesicular lipid traffic - formed by 'bridging complex' proteins that bind the membranes of both structures. The membranes come so close together in ER junctions that the LTP's are able to bind to both the donor and acceptor membranes simultaneously for highly efficient transfer between the two membranes - grab and release lipids as they use their flexible 'hinge to swing between the donor and acceptor membranes

Answer 67

- The mitochondrial circular DNA (cDNA) contains only 37 genes, but the mitochondrion has ~1000 proteins; Therefore, most mitochondrial proteins are coded by nuclear genes and are imported into the mitochondria. -Mitochondrial import occurs at outer/inner membrane contact sites (eg. the components involved are brought in close contact such that the transfer of the protein occurs over a short distance without membrane fusion). - impaired mitochondrial structure, which leads to impaired energy production, causes mitochondrial myopathy whose clinical signs (poor muscle control/posture and cognitive impairment) are mostly the result of globally inefficient ATP production in cells with high metabolic rates (eg muscle cells and neurons).

Answer 68

I) Chaperones bind the polypeptide to be imported in the cytoplasm and transports it to the mitochondrion. II)A mitochondrial targetting sequence in the polypeptide directs it to the Translocon of the Outer Membrane (=TOM) complex which is a large transmembrane channel that drives the polypeptide through the outer membrane into the intermembrane space of the mitochondrion. III/IV) The small Translocon of the Inner Membrane (=TIM) complex, which is a peripheral membrane, binds the polypeptide delivers to the large TIM complex, which is a large transmembrane protein complex that inserts the polypeptide into the inner mitochondrial membrane membrane. V) Polypeptide is released into the membrane and it folds into its native structure.

Answer 69

- Small, membrane bound organelles; self-replicating; important in regulating metabolism in all cells (eg. ß-oxidation-mediated breakdown of fatty acids which generates Acetyl-CoA that is utilized in the citric acid cycle in the matrix of the mitochondria). • All proteins are trafficked/transported to peroxisomes as they have no genetic material via: 1) A peroxisomal targeting signal sequence in the protein that targets cytosolic proteins to the peroxisomal membrane in a manner similar to protein targetting to the mitochondria; 2) From the ER by fusion with ER-derived vesicles. • Peroxisomal defects affect many tissues, often severely (eg. Zellweger's Syndrome is caused by an impairment of peroxisomal protein import that causes death shortly after birth).

Answer 70

Form a 3D network of protein filaments that act to maintain cell morphology, move intracellular components (e.g. vesicles and organelles), and facilitate the movement/ migration of entire cells - 3 main classes

Answer 71

~6nm diameter • 'Thinnest' cytoskeletal element; formed of filaments called F (fibrous)- actin which are comprised of two chains of globular actin monomers (= G actin). - filaments are dynamic with plus (faster growing) ends and minus (slower growing) ends. - Capping proteins regulate the length and speed of growth. - Filaments can be bundled together for different functions, and bundles are maintained by different actin filament binding/stabilizing/cross-linking proteins (eg. α-actinin) - Myosin motors can attach to F-actin to either initiate contraction (both in muscle and non- muscle cells) or move cargo (vesicles). - Focal adhesions are regions where the actin cytoskeleton binds/adheres to the extracellular matrix (ECM) across the plasmamembrane (Fig 2.32). • F-actin in 'stress fiber' bundle of f-actin are linked to the cytoplasmic domains of transmembrane integrins by a scaffold of stabilizing proteins (eg. vinculin and talin). - The extracellular domains of the integrins then bind extracellular matrix molecules (eg fibronectin, laminin or collagen). - These attachments are critical for cell adhesion and migration (ie. during embryogenesis, tissue formation, wound-healing and many organ system functions). - can also be linked together into gel-like webs and networks by 'scaffolding' proteins such as cortactin and filamen in the outer portion/cortex of the cell. These actin networks are critical for cell shape and, therefore, are very important for the form and function of tissues.

Answer 72

(8-10nm in diameter): • Filaments are 'intermediate' in diameter and formed by overlapping protein rods. • Form structural scaffolds within the cytoplasm (eg. cytokeratins) and the nucleus (eg. lamins)

Answer 73

(25 nm in diameter): • Hollow tubes comprised of 13 protofilaments fromed from globular α- and β- tubulin heterodimers that have a '+' (plus) 'growing' end where dimers can be added to increase the length of the tubule • Originate at the centrosome from γ-tubulin ring complexes = the '-' (minus) o Centrioles are specialized microtubular structures within centrosomes, nucleate microtubules and generate the long spindles that attach to chomosomes during mitosis • Microtubules also critical for movement of organelles in the cell, and for the movement of specialized cellular projections (eg. cilia and flagerlla) as well as chromosomal segregation • 'Kinesin' motor proteins bind cargo and move along microtubules towards the plus end, whereas 'dynein' motor proteins move toward the minus end of the microtubules.

Answer 74

- nuclear structure: euchromatin (light patches in figure, unwound DNA that can be effiently transcribed); heterochromatin (densely packed, not being transcribed); nuclear envelope; and nuclear pores, which are large protein assemblies embedded in the nuclear envelope; • Nuclear pores have a size of 9-11nm and allow small molecules to pass freely in and out of the nucleus. Larger molecules must be tranported in (import) and out out (export) of the nucleus. Thus, the number of nuclear pores correlates with the metabolic activity of the cell

Answer 75

- The major concept here is that the RanGTPase, is maintained in two different states depending on location: in the cytoplasm it is GDP-bound ('off'); in the nucleus it is GTP- bound ('on') - In the cytoplasm cargo proteins with a 'Nuclear Localization Signal' (NLS) interact with the importins which leads to their movement through the nuclear pore as a complex into the nucleus - Once in the nucleus RanGTP binds the cargo/importin complex (via importins' 'Nuclear Export Sequence [NES] and the cargo is released; RanGTP/Importin are then exported out of the nucleus - In the cytoplasm the 'GTPase activating proteins ('RanGAPs') convert RanGTP to RanGDP. This turns the Ran 'off' such that it releases the importin proteins so that they can begin the cycle again with new cargo proteins - RanGDP, which is small in size diffuses back through the nuclear pore. In the nucleus, Ran Guanine Exchange Factors (RanGEFs) convert RanGDP to RanGTP so that it is once more 'on' and ready to export importins (or any other proteins in the nucleus with an NES sequence) once again.

Answer 76

DNA damage (ie. genetic mutation) activates the portin 'p53' which then induces production of the p21 protein that then inhibits the CyclinE/CDK2 complex such that the cell does not move from G1 to S. This gives the cell a chance to repair the DNA damage/mutation. If it cannot, p53 can then direct the cell to undergo apoptosis via the 'intrinsic' pathway.

Answer 77

• Active 'programmed cell death' • Reduces inflammation due to debris release that occurs after unprogrammed, passive death by 'necrosis' • Important in controlling cell numbers in development (e.g. cell removal during toe and finger formation in the hands and feet) and in responding to cellular damage or pathological processes by clearing damaged cells (eg. tissue damage). • Two major types of Apoptosis

Answer 78

- initiated by extracellular death ligands (ie. come from outside the cell and therefore are 'extrinsic') that bind to death receptors and initiate signaling pathways that activate the executioner caspases that cause a breakdown of the cytoskeleton, membrane blebbing and chromosomal digestion cleavage and cell death.

Answer 79

- initiated by intracellular stresses such as DNA damage (and therefore occur inside the cell = 'intrinsic') that initiate the release of cytochrome c from the mitochondria that activates the 'apoptosome' that ultimately activates the executioner caspases cytoskeletal breakdown, membrane blebbing, chromosome digestion and cell death. - There is some cross talk between the two pathways such that the activation of one pathway can ultimately activate the other pathway.

Answer 80

- Cell junctions facilitate the formation of tissues by aggregating individual cells with each other and their associated extracellular matrix (ECM) • Cell junctions are an especially prominent feature of epithelial cells. All of the examples in this lecture are found in epithelia - Cell junctions occur at points of cell-cell or cell-ECM contact

Answer 81

• Anchoring - mechanically attach cells to other cells or the ECM • Occluding - seal the contacts between neighboring cells • Channel-forming/communicating - form channels between cells for communication/allow chemical and electrical signals to pass from cell to cell

Answer 82

- transmemebrane adhesion protein - adapter protein - cytoskeletal linkers

Answer 83

These are integral membrane receptors that span the cell membrane to connect the inside and outside environment of the cell. The outer extracellular region attaches to other adhesion proteins on neighbouring cells (cell-cell adhesion) or extracellular matrix molecules (cell-ECM adhesion). Their inner intracellular regions attach to cytoplasmic 'adapter' proteins and connect to other proteins like cytoskeletal linkers and cytoskeletal proteins themselves (eg. actin). Transmembrane proteins are classified by how many times they cross the membrane: single pass, two pass, three pass transmembrane protein, etc.

Answer 84

They bind to the adhesion complex at the membrane, recruit additional components to the adhesion complex and regulate the adhesion complex.

Answer 85

physically link between the adhesion complex proteins to the cytoskeleton

Answer 86

1. Made up of multi-protein complexes 2. 'Clustering' of the transmembrane adhesion proteins in the plasmamembrane - the combined strength of multiple bond interactions increases overall strength of the junction that binds to either other cells or the extracellular matrix 3. The clustered adhesion proteins link to the cytoskeletal network inside the cell which produces a huge tension-bearing protein interaction network running through the tissue.

Answer 87

Positional asymmetry (eg. regional differences) within the cell

Answer 88

- apical - lateral - basal

Answer 89

this is the free, unattached plasma membrane region that faces an open space (eg. 'outward') that may be air-filled (eg. parts of the respiratory tract) or fluid- filled (eg. blood).

Answer 90

this is the membrane region that is in close contact with neighbouring cells within the epithelium

Answer 91

his is the domain that is attached to extracellular matrix that often faces underlying connective tissues (eg. 'inward')

Answer 92

carbon/platimum 'casts' are made of frozen membrane surfaces, make it possible to view adhesion protein clusters embedded in the membrane as well as their associated adaptor proteins and linker proteins. For examination purposes in this course you will not have to distinguish between 'E' and 'P' faces on a freeze fracture electron micrograph.

Answer 93

- Tight Junctions/Zonula Occludens - Adherens Junctions/ Zonula Adherens - Desmosomes/Macula Adherens - Gap Junctions/Communicating Junctions

Answer 94

- belt that goes all the way around the cell. • Tight junctions are located very near the apical domain of polarized epithelial cells and they join neighbouring cells very closely together. • Formed by strands of interacting transmembrane proteins observable by freeze-fracture electron microscopy. Two core tight junction proteins are Claudin and Occludin. Specifically, tight junctions are formed by the transmembrane adhesion proteins Claudin (for tight junction formation) and ‘Occludin’ (for barrier function, but not needed for maintaining the overall tight junction structure) binding to the same type of molecule on neighbouring cells (i.e. Claudin- Claudin or Occludin-Occludin interactions). • Barrier permeability can be tested by using a dye/tracer that is added to either the apical or basal side of the epithelium and observing whether the dye/tracer diffuses over the junction • Tight junctions control diffusion of material between cells (ie. along the lateral membranes). This is very important physiologically as it sets up epithelia as 'barriers' where transport of molecules (eg. glucose for example, across the intestinal epithelium) can be highly regulated through the cells based on polarized insertion of specific plasma membrane transporters in the apical and basal domains

Answer 95

Loss of the tight junction adhesion protein Claudin-16 (due to mutation of one of many claudin genes) disrupts the kidney's ability to efficiently transport electrolytes out of the urinary filtrate. As a result calcified deposits form within the kidneys (= white dots in the CT scans shown in the lecture powerpoint) which can eventually lead to blockage and kidney failure.

Answer 96

Form strong continuous adhesion belts around the cell (covering the entire circumference) on the lateral domain just basal to tight junctions • Important for the formation of 2-dimensional sheets of epithelial cells than line our body compartments. • They are composed of single-pass transmembrane adhesion proteins called 'classical cadherins'.

Answer 97

1. At low calcium levels two cadherin molecules interact with each other on the surface of the same cell to form 'cis-homodimers' 2. Calcium-binding to the extracellular domains of the cis-homodimers causes them to undergo a conformational change and 'straighten' 2. Cadherin straightening promotes "trans" homodimerization, which means that a cadherin cis-homodimer on one cell then binds another cadherin cis-homodimer located on the surface of another cell (ie. this initiates adhesion). 3. This trans-bound complexes cluster together in the plane of the membrane (ie. this starts to stabilize adhesion). • Cadherin clusters then link to the actin cytoskeleton via intracellular anchoring complex containing adapter and linker proteins called "catenins" (these strengthen the adhesion between cells).

Answer 98

A loss of cadherins can contribute to the formation of, and the metastatic progression of, cancers that arise in epithelium (= 'carcinomas'). A hallmark of a carcinoma is the loss of epithelial structure which is often associated with the loss of cadherin (by mutation and/or transcriptional repression). This facilitates a loss of cell cycle control that causes the inital 'primary' tumor to form. A loss of cadherins can also facilitate the dissociation of tumor cells from each other which helps initiate 'tumor invasion' which is the first step in metastasis that ultimately leads to the progressive formation of tumors at seconday sites that is a major cause tumor mortality. The process of carcinoma-associated cell dissociation and invasion has many things in common with the epithelial-to-mesenchymal transiition [EMT] that occurs when mesenchymal cells to break away from the epiblast and invade the space between the developing ectoderm and endoderm during gastrulation).

Answer 99

- Macula = spot; these are small spotlike-junctions that form along the entire lateral domain of cell types in tissues that are exposed to tensile forces/mechanical stress like skin • Desmosomes are junctions that are based on adhesions between cadherin-like receptors called Desmocollin (Dsc) and Desmoglein (Dsg), which bind to cytoskeletal linkers to connect with the keratin family of intermediate filaments. Keratin intermediate filaments are stronger than the actin filaments found in adherens junctions.

Answer 100

Pemphigus vulgaris - A loss of dsg causes a loss of adhesion between layers of the skin, resulting in skin blistering.

Answer 101

Major function is to allow communication and sharing of small molecules (eg. ions, signal transduction membranes and some nutrients) between neighboring cells • Connexin are the gap junction adhesion proteins. Six connexins cluster together as a hexamer called a connexon in the lateral membrane domain of one cell membrane. A connexon will then bind a similar hexamer/connexon in the lateral membrane domain of a neighbouring cell to form a functional channel between the cells that can be regulated (ie. can be opened or closed) and can pass small molecules between linked cells in the tissue (=communication).

Answer 102

Vohwinkel Syndrome (keratodema) - Loss of connexin-26 (= one of many isoforms of connexin) causes a disruption of communication between epidermal cells in the skin. This causes the skin to overproduce keratin and thus it becomes hard and thick (= keratodema).

Answer 103

secreted by cells into their outside environment. It is critical for cells to organize into tissues and it contains significant amounts of proteins and complex polysaccharides, and has multiple functions.

Answer 104

- Ground substance | - Fibers

Answer 105

- Glycosaminoglycans (GAGs) - Proteoglycans (PGs) - Glycoproteins (GPs)

Answer 106

- These are chains of carbohydrates (=glycan) that are negatively charged. Their negative charge attracts cations, particularly sodium, which in turn attracts large amounts of fluid that gives the ground substance its gel-like quality that is resistant to compression.

Answer 107

a GAG that is an anticoagulant

Answer 108

- a huge and abundant GAG, and it is the only GAG that does not bind proteins directly; it is lubricating and thus it is found in joints; it is also important in wound repair, cell migration, and inflammation

Answer 109

Mucopolysaccharidoses (MPS) diseases; Pleiotrophic meaning they can can have many effects including dwarfism, mental retardation, cardiomyopathy; Are caused by a failure to break down/remodell GAGs which occurs constantly in the connective tissues normally.

Answer 110

- These are proteins with many long, unbranched GAG chains attached to them - The attached GAG chains make up most of the molecule's mass (up to 95% carbohydrate by weight) - Aggrecan is a proteoglycan that is a major component of cartilage that serves to aggregate GAGs, other proteoglycans, glycoproteins, and fibers (eg. collagen) to form a deformable molecular meshwork in the specialized ECM of cartilage

Answer 111

- proteins with numerous short, branched oligosaccharide chains added to them. They are 1 - 60% carbohydrate by weight. Therefore, most of their mass is usually the protein itself (ie. there is less sugar attached to GPs than PGs) - Fibronectin is a glycoprotein found in many ECMs, and is a key molecule in blood clotting and tissue repair - Laminin is a glycoprotein that is prominent in Basement Membrane ECM's that associate with epithelia specifically

Answer 112

- long polymers of proteins, are embedded within the ground substance; they can be seen running through the ground substance of the ECM in electron micrographs or with special staining in light micrographs. They are mainly composed of two proteins: collagen and elastin in connective tissue ECM. Fibers function to provide structural support.

Answer 113

It's the main ECM protein; makes up about 25% of proteins present in the body • It's flexible, but strong and resistant to stretching • A collagen polymer is composed of repeating units of tropocollagen, which is a helix of three α-chain subunits. - There are 29 different collagen genes in humans -Inelastic/don't stretch; critical for tensile strength of connective tissues

Answer 114

stretchy/distensible and flexible, and is the main component of structures known as elastic fibers. In ECM's where elastin fibers are prominent this gives the tissue the ability to ability to change form under tensional loads and then return to the original form when that load is removed

Answer 115

- made up of an extensive mesh-like network composed of interlinked GAGs, PGs, GPs and fibers. - contains fibroblasts, which synthesizes and secrete the precursors of all components of ECM and collagen fibres, and adipocytes, chrondroblasts, osteoblasts, tendon cells, etc.

Answer 116

• Specialized ECM that forms a carpet-like structure located at the interface between epithelia and the underlying connective tissues • It is a mechanical barrier between epithelial and connective tissues, an anchoring point (firm and flexible support) for the epithelial cells that attach to it via 'hemidesmosomes' (see below), and a molecular filter for the epithelium. • It consists of two parts: 1) Basal Lamina 2) Lamina Reticularis

Answer 117

- produced by the epithelial cells; it consists of two layers: 1) Lamina Lucida 2) Lamina Densa - Laminin binds collagen and integrins and acts as a bridge between the two layers

Answer 118

Contains mainly the GPs laminin (ECM glycoprotein that binds to both integrins and fibers of the lamina densa) and integrins (ECM-binding adhesion receptors, see below). This is the 'clear" portion of the basement membrane on transmission electron micrographs

Answer 119

A mixture of fibers (mostly type IV collagen), the PG 'perlecan' and the GAG 'heparin sulfate' that form a network that gives the basement membrane carpet its tensile strength. This is the 'dark' (eg. electron dense) portion of the basement membrane on transmission electron micrographs.

Answer 120

• Produced by connective tissue cells • Contains collagen I and III, the GP 'fibrillin' and anchoring fibrils (type VII collagen fibers). These anchoring fibrils reach up into the basal lamina above and down into the connective tissue ECM below to hold things together • Can be thought of as the spiky/sticky/tack-like bits of the basement membrane that holds the carpet onto the underlying connective tissue ECM • Clinical relevance: Alport syndrome - caused by mutations in collagen IV and therefore affects basement membrane structure; becomes progressively worse with age leading to kidney failure, hearing loss, and cataracts.

Answer 121

• These structures link/attach cells to the ECM • Their are overall molecular architecture is similar to cell-cell junctions (see Lecture 7) in that they consist of: • Cell adhesion molecules • Linker/adapter molecules that bind both the adhesion molecules and the cytoskeleton • Cytoskeletal molecules • The difference, however, is that the cell adhesion molecules (the main one being integrins) bind to ECM glycoproteins and fibers rather than cell adhesion molecules on other cells.

Answer 122

• Transmembrane/integral membrane protein 'heterodimers' that are made up of two different subunits designated 'alpha' (18 in humans) and 'beta'. (8 in humans) • There are many different combinations of alpha/beta dimers which gives individual integrins a specificity for binding to many different ECM 'ligands' that include fibers (eg. collagens) and glycoproteins (eg. laminin, fibronectin) and, in the case of activated platelets, 'fibrin' in clotted blood • Integrins exist in two states: low affinity and /high affinity states with respect to ECM binding. • Integrins are activated in two ways: a) "outside-in": by the binding of ECM ligands just outside the cell which pulls on the integrin and opens it up to the active state, or b) "inside- out": by integrins binding proteins inside the cell that pull on them and move them into a high affinity state - these shifts between inactive and inactive states are 'tuneable' between the two states • After ligand binding integrins can also cluster just like other cell adhesion molecules do - see slide titled 'The integrin adhesion complex'. This increases the strength and stability of the cell-ECM adhesion. • Functions: cell migration; cytoskeletal organization, signal transduction modification; attachment of tendons to muscles; ligaments to bone; attachment of epidermis to dermis in the skin

Answer 123

- Link to actin • These adhesions are found in many cell types • Made up of a variety of integrin heterodimers • They are often very dynamic and they can be used to generate traction forces on the ECM (ie. can 'pull' on it due to the actions of motors such as myosins on bundles of actin filaments called 'stress-fibers that are attached to these adhesions). Therefore, focal adhesions are critical for cell movement/migration. • Stable forms of these adhesions are important for muscle attachment to tendons (which are made up mostly of collagen fibers; see Lectures 12/13). This relationship has been examined experimentally in 'fruit flies' (Drosophila), a model organism where the individual molecular components of the muscle/tendon attachment can be easily manipulated genetically

Answer 124

- Link to intermediate filaments - These specialized adhesions are found in epithelial cells exclusively. - Make up of α6β4 integrin heterodimer - They bind the basal surface of polarized epithelial cells to laminin in the underlying lamina lucida of the basement membrane ECM. Thus, they are very stable, anchoring junctions. The stability and anchoring function of these junctions is facilitated by the interaction with strong and stable intermediate filaments. The stability of these junction is also facilitated by the extremely long intracellular/cytoplasmic tails of alpha6/beta4 integrins. - On a transmission electron micrograph hemidesmosomes look like 'half a desmosome', which is how they originally got their name.

Answer 125

'Junctional epidermolysis bullosa' is an extreme skin blistering disease, that is caused by the loss of β4 integrin. Thus, epithelial cells (ie. skin keratinocytes) cannot anchor properly to the underlying laminin in the basement membrane. As a result the epithelium of the skin lifts and blisters when any tension or extreme movement is applied to it.

Answer 126

a. Continuous layer(s) of cells stuck together with no extracellular matrix between them. Connection are mediated through cell-cell junctions such as desmosomes, tight junctions and gap junctions b. Attached to the basement membrane through hemidesmosomes Stem cells often reside on the bottom layer connected to the basement membrane c. No blood vessels (avascular), nutrients and waste transported by diffusion

Answer 127

a. Act as a protective covering over tissue b. Regulate transport through tight junctions and channels/transporters/pumps c. Absorption from extracellular environments (i.e. using channels, transporters and pumps inserted in apical and basolateral membranes) d. Secretion (Glands) - exocrine, paracrine, endocrine

Answer 128

Claudin/Occludin proteins | - paracellularly (between epithelial cells) transport

Answer 129

transcellular (across cell) transport

Answer 130

All 3 germ layers (Endoderm, Mesoderm, Ectoderm)

Answer 131

- secrete to the outside ducts and free surfaces (apical secretion)

Answer 132

- secretes to underlying connective tissue (basal secretion) that produces a local effect

Answer 133

- secretes to underlying connective tissue (basal secretion) and into the bloodstream where secreted product travels to, and acts at, distant sites (basal)

Answer 134

- basal membrane attachment and cell -cell junctions

Answer 135

- Adherens and tight junctions toward the apical side i. polarity protein complexes associate with terminal bars to direct vesicle traffic apically or basolaterally depending on sorting sequences ii. Actin filaments at terminal bars form a zonular “belt” apically all the way around the circumference of the cell iii. Myosin can contract the actin belt to constrict the cells apically; Apical constriction the decreases the apical cell diameter while increasing basal cell diameter; collectively this 'bends' the epithelium and helps generate the formation of tubes (=morphogenesis)

Answer 136

i. Very small 1um long 25nm wide projections on apical surface. Viewable by E.M. but not individually by L.M.; collectively can be seen as a 'brush border' on the apical aspect of the epithelium by L.M. ii. Actin filament core that extends into cell and connects together at terminal web ( anchored to zonula belt) iii. Increases surface area for absorption (prominent in the small intestine for absorption of the products of digestion) iv. Not motile

Answer 137

i. Larger; 10um long, 250nm wide projections on apical surface. Individual cilia viewable by both E.M. and L.M. ii. Microtubule core linked together by radial spokes (9,2 arrangement) action of microtubular motors actively bends cilia = motility iii. Collective ciliary motility produces a beating pattern across the top of epithelia to move material across it (prominent in the respiratory system for debris clearance)

Answer 138

1 layer, all cells are attached to basement membrane

Answer 139

More than 1 layer not all cells are attached to basement membrane

Answer 140

Appears to be many layers but all cells are attached to basement membrane

Answer 141

Flattened cells

Answer 142

Cube-shaped cells

Answer 143

Taller than wide-shaped cells

Answer 144

apical cells can change shape from pillow-like to squamous depending state of stretch/distension of the epithelium

Answer 145

- Lining epithelia at locations of gas exchange (eg. inner blood vessel lining, body cavity lining, loops of henle, alveoli blood air barrier

Answer 146

- Secretion, absorption, protection (eg. Ducts and kidney tubules)

Answer 147

- Transportation, absorption, secretory. Often have microvilli (eg. digestive and urinary tracks)

Answer 148

- protective and waterproof, apical most layers consist of enucleated/dead cells that contain large amounts of keratin (= squames; found in the epidermis of the skin)

Answer 149

protective, found in wet areas of transition between external and external transition of the body (eg. GI, Respiratory and Genitourinary tracts).

Answer 150

Multifunctional; cells are of different heights from cuboidal to tall columnar; appears multilayered due to nuclei at multiple levels by L.M. but all cells attach to the basement membrane; thus, actually a modified simple epithelium; often ciliated and is prominent in the respiratory system

Answer 151

Truly stratified and distensible/stretchable; apical-most cells change shape as the epithelium becomes distended due to dynamic cell-cell junctions and pleating/folding of plasmamembrane between junctions; prominent in bladder and ureter which are often distended/stretched as they fill

Answer 152

-very thin specialized form of collagen (Collagen Type III) fibers that are cross-linked together to form a meshwork/net within highly cellular connective tissues (eg. within lymphoid organs)

Answer 153

- pleuripotent mesenchymal stem cells (in the connective tissues) or pleuripotent hemopoietic stem cells (in the bone marrow; cells then travel to connective tissues through the bloodstream)

Answer 154

Fibroblasts, adipocytes, pericytes, mast cells, macrophages, plasma cells

Answer 155

- Loose/Areolar CT - Dense CT - irregular and regular - Adipose CT - Reticular CT

Answer 156

many cells, abundant ground substance; few fibers; flexible not resistant to stress

Answer 157

few cells/more fibers; resistant to stress

Answer 158

fibers/strength in all orientations directions

Answer 159

fibers in parallel arrays, strength in one direction

Answer 160

high number of adipocytes grouped into lobules separated by dense irregular CT 'septae'

Answer 161

highly cellular connective tissue with interwoven reticular fibers

Answer 162

- epithelial portion is secretory (= parenchyma) - connective tissue portion is inductive and supportive (= stroma) - exocrine glands, secretory product is released apically into a duct or onto a free surface - endocrine glands, secretory product is release basally into stroma, picked up bloodstream (= 'hormone); factors that act locally on nearby cells after diffusing within the same tissue are called 'paracrine' factors

Answer 163

- unicellular glands = single cells embedded in a surface/lining epithelium (eg. goblet cells) - multicellular glands = clusters of secretory parenchymal cells surrounded by stroma; secrete into a duct (eg. salivary glands)

Answer 164

- duct morphology (simple = unbranched ducts; compound =branched ducts) - secretory portion morphology (tubular=same diameter as duct; acinar/alveolar=expanded diameter compared to duct) - nature of secretion (serous = proteinaceous, enzyme rich; mucous = proteoglycan, lubicricating)

Answer 165

- supports soft tissues - provides a low friction sliding area for joints - promotes growth of long bones as a reserve of new bone deposition at the 'growth plates' of endochondral bones

Answer 166

- Chondroblasts start to deposit cartilage ECM in the outer portion of the tissue, arise from chondrogenic 'chondroprogenitor' cells located in the outermost 'perichondrium' connective tissue layer - Chondrocytes are terminally differentiated from chondroblasts and are embedded in lacunae (small spaces) located deep within the tissue

Answer 167

- Generally, water>collagen>proteoglycans; resilient/plastic/deformable, but resists compression - Intermediate thickness Type II Collagen fibers provides limited tensile strength - Avascular; therefore high diffusion rates through hydrated matrix is critical for cell survival

Answer 168

(1) Hyaline cartilage (HC) (2) Elastic cartilage (EC) (3) Fibrocartilage (FC)

Answer 169

- Type II collagen fibers predominate - 60-70% water, recruited by significant amounts of proteoglycans (PG) - Well-defined perichondrium, with limited regenerative potential - Found in joints, nose and trachea (most prevalent type of cartilage)

Answer 170

- Decreased matrix/increased number of cells compared to hyaline cartilage - Type II collagen + Elastic fibers present in the matrix - Well-defined perichondrium, with limited regenerative potential. - Found in very flexible areas (eg. outer ear)

Answer 171

- Matrix contains high amounts of thick, strong Type I collagen fibers = very high tensile strength compared to other type of cartilage - Also has a number of characteristics of dense regular connective tissue with some chondrocytes in lacunae and some proteoglycans's that give some resistance to compression - No distinct perichondrium = very, very low regenerative potential - Found in intervertebral disks, pubic symphysis, and sites of tendon insertion/attachment to bones, cushioning meniscus in some joints (eg. knee cartilage that is often 'torn')

Answer 172

- Osteoblasts: deposit osteoid (organic ECM), arise from osteogenic 'osteoprogenitor' cells in outer 'periosteum' connective tissue (note: some osteogenic cells can migrate in, with blood vessels, to the inner surfaces of bone that face the central marrow cavity (= 'endosteum') - Osteocytes: fully differentiated from osteoblasts trapped within lacunae deep in the mineralized/rigid bone matrix - Osteoclasts: resorb/breakdown bone matrix; multinucleate and derived from 'hematopoietic stem cells'; Understand how ostoclasts breakdown of both the inorganic and organic portions of matrix (regulated by hormones from parathyroid and thyroid glands

Answer 173

- Initially laid down by osteoblasts. - Organic ('osteoid'): high in type Type I Collagen = strong thick fibers= the 'rebar' reinforcement of the bone ECM - Inorganic (mineralized'): contains hydroxyapatite (calcium phosphate crystals) for rigidity = the 'concrete' portion of the bone ECM

Answer 174

- Periosteum covers external surface of bone; contains osteogenic cells with considerable regenerative potential; - Inner Spongy Bone - Outer Compact/Cortical Bone

Answer 175

made up of spicules/small spikes (also known as 'trabelulae) that are in contact with the bone marrow/; remodelled by 'pitting' by osteoclasts; pits/depressions/shallow lacunae; lacunae can subsequently be filled in by osteoid deposited by osteoblasts.

Answer 176

- structural units (='osteons') formed by concentric layers of dense, bone tissue that form a cylinder with a central 'Haversian' canal o Harversian canals contain blood vessels that run the length of the osteon o Volkmann's canals are tunnels that run perpendicular to, and connect, the Haversion canals between different osteons (see ppt slide and Fig 7-10 of textbook); both have blood vessels (and nerves) running through them o Note: individual osteocytes in the bone tissue form very small canals/tunnels (='canaliculi') that contain long, extended cell process; these canaliculi connect from osteocyte to osteocyte via gap/communicating junctions

Answer 177

- Intramembranous | - Endochondral

Answer 178

- generates flat bones, most prevalent in skull: forms directly in mesenchyme, which condenses and generates osteoprogenitor cells which then differentiate and lay down bone matrix

Answer 179

- generates most bones in body - forms within a pre-formed cartilage scaffold; 'ossification centers' form in which bone replaces cartilage within the scaffold; the central ossification center is the 'diaphysis', the outer ossification centers are the epiphyses; throughout childhood and puberty a zone of reserve cartilage (= 'epiphyseal plate' or 'growth plate') remains; the growth plate can proliferate (ie. increase in size) and then gradually ossify/become bone; the growth plate proliferates in response to growth hormone from the pituitary.

Answer 180

- degenerative loss of articular hyaline cartilage, cannot be regenerated as cartilage leads to bone coming into contact with bone = painful and loss of joint stability (common with age and 'wear and tear'; very different from rheumatoid arthritis which is caused by chronic inflammation within the joint which leads to cartilage destruction secondarily.

Answer 181

- bone homeostasis shifts towards resporption (loss) rather than deposition (gain) of bone ECM; this is prevalent in post-menopausal women as estrogen stimulates deposition; often treated pharmacologically by inhibiting the activity of osteoclasts.

Answer 182

• Mesodermally-derived. • Can be striated (eg. striped due to sarcomeres; visible by L.M.) or non-striated (eg. no fully organized sarcomeres, but still contractile). • There are two types of striated muscle (eg. skeletal and cardiac muscle). • There is one type of non-striated muscle (eg. smooth muscle). • Muscle contraction can be voluntary or involuntary. • Functions: locomotion/movement, maintenance of posture, respiration, constriction of viscera (eg. rhythmic contraction = 'peristalsis' in GI and Genitourinary tracts), constriction of blood vessels, heart beat; to do so they must be contractile (=shorten) which is actin- myosin based. • Note: in muscle, many structures are prefaced with the term 'sarco'; thus sarcoplasmic reticulum = endplasmic reticulum in muscle cells

Answer 183

• Striated, voluntary. • Myofibers (= skeletal muscle cells) are multinucleate (with nuclei at the periphery) and contain myofbrils organized into myofibrils; cells are bundled together as groups = fascicles. • Individual myofibers attach directly to a surrounding basal lamina ECM which is similar to the basal lamina that epithelial cells attach to; muscle cell attachment to the basal lamina is cell-ECM junction based and is mediated by the dystroglycan complex (see Ch 4, pg 83 and Lecture 13). • Layers of connective tissue then surround the muscle: endomysium = fine sheath of reticular that surrounds individual myofibers; perimysium = dense irregular (collagenous) connective tissue that surrounds fascicles; epimysium = dense irregular (collagenous) connective tissue that surrounds the entire muscle . These connective tissue investments hold the muscle together during cycles of contraction and relaxation. • Ends of muscle fibers attach to dense regular collagen fibers of tendons via finger-like extensions; this attachment is mediated by cell-ECM junctions where the adhesion molecules are integrins. • The cells of skeletal muscle are the myofibers, which are multi-nucleated long, cylindrical and striated with nuclei located at the periphery/edges of the cell

Answer 184

- Plasmamembrane = sarcolemma - Cytoplasm = sarcoplasm - Well-developed endoplasmic reticulum = sarcoplasmic reticulum - Parallel arrays of thin actin and thick myosin myofilaments that are bundled in parallel arrays = a myofibril (note: there are many myofibrils within a single skeletal myofiber) - Each myofibril is surrounded by mitochondria, sarcoplasmic reticulum (muscle ER), the terminal cisternae (= expansions) of the sarcoplasmic reticulum, and deep invaginations of the sarcolemma that are perpendicular to the length of the myofiber (=T tubule) (see Fig 8.5). Two terminal cisternae of the sarcoplasmic reticulum and a single T-tubule come very close together to form a triad (see more below).

Answer 185

* Stores intracellular calcium (when the muscle is at rest); releases calcium into the sarcoplasm when the muscle is stimulated by motor neuron firing. * The SR is a modified smooth ER (eg. devoid of ribosomes) that forms an interconnected network of tubules. * Two expanded sacs of the SR (= 'terminal cisternae') are very closely opposed to deep invaginations of the sarcolemma (=T-tubules) to form a triad. Therefore, the 'triad' is actually a specialized 'ER junction'. * A membrane depolarization/impulse generated by motor neurons that interact with the myofiber travels along the sarcolemma into the T-tubule...This stimulates the terminal cisternae to release calcium into the sarcoplasm very near the myofibrils....This stimulates the contraction of the sarcomere.

Answer 186

• One sarcomere is defined as the small region of a myofibril between two successive Z discs where thin actin filaments insert (see also text page 160 for description of A-band, M-line and I-band). • The sarcomere contains thick (myosin) and thin filaments (actin). Myosin: coiled-coil myofilament composed of two heavy chains, each with a globular head at the N-terminus, and four light chains. Actin thin myofilaments: has tropomyosin, actin, and troponin complexes, which bind calcium. • The thin filaments originate/are physically linked to proteins in the Z disk and project toward the center of the sarcomere (see Fig 8.8). • The thick filaments form parallel arrays that cross the center of the sarcomere and partially overlap with the thin filaments. • In the relaxed state, the thin filaments do not reach the midline and the thick filaments do not extend the entire length of the sarcomere (ie. they don’t reach/attach to the Z disk) • During contraction, individual thick and thin filaments do not shorten. Instead, the two Z disks are brought closer together as the thin filaments slide past/are pulled over the thick filaments towards the center of the sarcomere (eg. Huxley’s sliding filament theory, see pg 162 of textbook).

Answer 187

- binding myosin head to actin | - Skeletal Muscle Contraction

Answer 188

1. Upon stimulation, the sarcoplasmic reticulum releases calcium into the sarcoplasm. Calcium binds 2. Tropnin binds cacium which changes its conformation/shape 3. Tropomyosin, which is attached to troponin, changes its position on the actin filaments. This shift unmasks the myosin-binding sites on the actin. 4. Myosin heads can now bind actin filaments.

Answer 189

1. ATP hydrolysis (ATP is split to ADP and inorganic phosphate ‘Pi’) causes the cocking of the myosin head to occur, and the myosin head is in its high-energy configuration. 2. Myosin attaches to the actin myofilament (in a calcium-dependent manner as described above). 3. As ADP and Pi are released, the myosin head bends as it pulls on the actin filament, dragging it to the center of the sarcomere. 4. As a new ATP attaches to the myosin head (low-energy configuration), the myosin head detaches from actin. 5. As a result the actin is pulled by the myosin towards the center of the sarcomere (ie. the thin actin filaments 'slide' over the thick myosin filaments

Answer 190

When a muscle is relaxed, actin and myosin filaments overlap slightly. When a muscle if fully contracted, actin filaments slide along the myosin, resulting in a great overlap and shortening of the sarcomere (ie. the Z-discs/lines come closer together = sarcomere and myofibril shortening

Answer 191

* The very specific immunostaining shows the axons (green; neurofilaments); blue (myelin sheath covering the nerve that ends before the axon terminal is reached) and the acetylcholine receptors in the sarcolemma/plasmamembrane of the end plate. * Upon depolarization due to an action potential traveling down the neuron, pre-synaptic vesicles containing the neurotransmitter acetylcholine (ACh) fuse with the axon terminal plasmamembrane in a SNARE-dependent manner. As a result, ACh is released into the synaptic cleft (= extracellular) where it binds to ACh receptors on the sarcolemma and triggers a depolarizing action potential that travels down the T-tubule; thisinduces Ca2+ release from the terminal cisteranae of the sarcoplasmic reticulum in the triad; the result is a contraction of the sarcomeres as described in Lecture 12. This process is known as T- tubule-based 'Excitation-Contraction Coupling'.

Answer 192

Is a multimeric toxin produced by the bacterium Clostridium botulinum that prevents the release of Ach from axon terminals by inhibiting the fusion of ACh-containing vesicles with the pre-synaptic axonal membrane at the neuromuscular junction (given that, you can probably deduce one of the molecular targets of the toxin - or you can check Wiki). Large amounts of botox leads to botulism that causes muscular paralysis, respiratory failure, and even death, because muscle contraction cannot occur. It is used cosmetically in much smaller doses to paralyze muscle contraction to decrease age-related 'wrinkling'

Answer 193

• Loss of function mutations in the scaffold/adapter protein 'dystrophin' causes the cell-ECM junction 'dystroglycan complex' to be released from the actin cytskeleton. This results in contraction-mediated damage/tearing of skeletal myofibrils. Ultimately, this leads myofiber cell death which leads to increased connective tissue deposition (=fibrosis/scarring and adipocyte) proliferation as well as inflammation within the muscle. - At the gross anatomical level this results in a swelling of the muscle = pseudo-hypertrophy. • Attempts to correct the defect are being made using viral-mediated transfer of the wild- type dystrophin gene into myofibers.

Answer 194

• Found exclusively in the heart • Cardiac muscle cells = cardiac myofibers = cardiomyocytes form the 'myocardium' (ie. the thick contractile walls of the heart's ventricles and the atria). • Cardiac myofibers are striated with true sarcomeric organization in myofibrils, but they are mononuclear (= one central nucleus per fiber) and their contraction is involuntarily controlled (fibers contract spontaneously with inherent rhythmicity). • Cardiac myofibers are short and branched and they attach to each other by intercalated disks • T tubules are present that have sparse amounts of sarcoplasmic reticulum associated with them (one tubule/one cistern = diad) that functions to release small amounts of calcium into the sarcoplasm upon depolarization. In addition, channels in the T-tubule membrane facilitate the passage of large amounts of extracellular calcium into the sarcoplasm to facilitate contraction after depolarization (see textbook pg 177/8)

Answer 195

1) Transversely-located (across the fibers at right angles) adherens junctions and desmsomes which are adhesive (ie. cardiomyocytes are attached to each other, usually at their branched ends (cardiomyocyes do not have myotendinous insertions like skeletal muscle myofibers as they do not attach to bone) 2) Laterally-located (parallel to the myofilaments) gap junctions which electrically couple the cardiac myofibers by allowing for rapid flow of information between fibers. This is important for the inherent rhythmicity of cardiomyocytes as it means that the stimulation of one cell can lead to the stimulation of neighbouring cells via gap junction transfer of ions).

Answer 196

• Found in the walls of tube-based organs/structures where their contraction decreases the diameter of the central lumen (eg. during rhythmic, peristaltic contractions in the gastrointestinal and urogenital systems; to decrease blood flow through small arteries and arterioles) • Smooth muscle myofibers are spindle-shaped and tapered each end, and they are mononucleated(= one nucleus per fiber). • Contraction is involuntary and is initiated by multiple contacts from the axons of neurons from the 'autonomic' nervous system ); there are no well-defined neuromuscular junctions. • Have no T-tubule-based excitation-contraction coupling; large numbers of gap junctions between smooth muscle myofibers allow direct electrical communication between adjacent smooth muscle fibers. This direct electrical communication facilitate slow rhythmic contractions across smooth muscle tissue. • There are no sarcomeres; therefore smooth muscle is not striated. • Cells have an extensive array of interweaving thin (actin) and thick (myosin) filaments that give some multi-directionality to the contraction (ie. they are arranged at oblique angles rather than in parallel arrays as is the case in skeletal and cardiac myofiber sarcomeres); thin filaments attach to aggregates of adapter/scaffold proteins called dense bodies that include actin bundling proteins (eg. alpha-actinin) and act as an anchor for the filaments (analagous to Z-lines in skeletal/cardiac muscle) • Contractile units consist of myosin filaments connecting to the actin filaments:

Answer 197

• Thick filaments (myosin) act on thin filaments to cause contractions between the dense bodies and dense plaques; this leads to shortening of the long, tapered, fusiform-shaped cells as well as some cell twisting. In histological sections this contractile twisting causes the nuclei to take on a 'corkscrew'-like appearance.

Answer 198

• Arteries and veins: in some of these blood vessels they are found in the central tunica media (see Lect 19 for more specific details) • Multiple layers in the wall of the stomach and intestines: that act together to generate peristalsis (= progressive and rhythmic contractions of the smooth muscle that propel food through the digestive tract); See Lect 27.

Answer 199

• The neuron is the functional cell of the nervous system that transmits this information. Therefore neurons have unique features that allow them to perform this function. • Nervous tissue develops from ectoderm. Some of the general functions of nervous tissue are: to detect and analyze sensory input; coordinate body activities, store (= learning) and recall (= memory) experiences • There are two parts of the nervous system: Central Nervous System (CNS) Peripheral Nervous System (PNS) • There is bi-directional information flow between the CNS and PNS.

Answer 200

• Consists of brain and spinal cord • Organized 'somatotopically' in that different brain areas are dedicated to serving/responding to different body parts and/or different modes or types of information • Certain body parts with fine motor and sensation capabilities (ie. oral cavity and hands) have a greater somatatopic representation in the brain (ie. there is more neuronal tissue = larger portion of the somatatopic 'map' that regulates or receives information from them). • Spinal cord: white matter contains tracts of myelinated axons where the information is ascending (ie. sensory information going up to the brain) or descending (motor information leaving the brain).

Answer 201

"bumps" on the cortical portion of the brain

Answer 202

"grooves" on the cortical portion of the brain

Answer 203

the precentral gyrus, which is located just anterior to the large central sulcus of the brain (where voluntary motor information originates in the brain)

Answer 204

the postcentral gyrus, which is the gyrus posterior to the central sulcus (where conscious sensory information first arrives in the brain)

Answer 205

neuronal cell bodies, dendrites, unmyelinated axons

Answer 206

tracts of myelinated nerve axons/fibers

Answer 207

• = All nerves of the body that are outside the CNS, often mixed motor and sensory nerves • Sensory component of peripheral nerves carry information from the body to the CNS = afferent nerves • Sensory/afferent fibers enter the spinal cord via dorsal nerve roots • Motor component of peripheral nerves carry information from the CNS to the body to effector organs (like muscles and glands) = efferent nerves • Motor/efferent fibers exit the spinal cord via ventral nerve roots (which was originally the 'floor plate' in the developing neural tube; see Lect03)

Answer 208

- somatic sensory nerves carry information that is consciously perceived. - somatic motor nerves carry information that leads to voluntary skeletal muscle contraction - consists of single neuron connection

Answer 209

-Sensory nerves receive unconscious 'propioceptive' (ie. regarding position of body in space) information -Motor nerves carry information that leads to the contraction of involuntary smooth and/or cardiac muscle, as well as the stimulation of the secretion of a number of glands - consists multiple neuron connections (synapses occur in peripheral autonomic 'ganglia') -The autonomic motor system further broken down into the sympathetic division (1st/preganglionic neurons originate in the thoracic and lumbar regions of the spinal cord; for 'flight/fright' in catabolic responses) and the parasympathetic division (1st/preganglionic neurons originate in the cranial, cervical & sacral regions of spinal cord; for 'rest/repose' in anabolic responses)

Answer 210

1) Neurons 2) Neuroglial Cells 3) Support Cells

Answer 211

from ectoderm/neuroectoderm | - excitable cells that carry out information transfer

Answer 212

from ectoderm/neuroectoderm - non-excitable cells that enhance efficiency of transmission

Answer 213

from mesoderm | - include cells of blood vessels (endothelium, fibroblasts) and microglia (immune cells of the CNS)

Answer 214

- soma - Dendrites - axon - Axon Terminal

Answer 215

cell body/perikaryon; has a nucleus with prominent nucleolus; the cytoplasm has cytoskeleton, organelles, Golgi apparatus, mitochondria, and ribosome-rich RER that stains with hematoxylin and, especially with Nissl stain (both are histochemical; bind acids)

Answer 216

receptive region of the cell = conduct impulses towards the cell body; has similar contents as the soma, with mitochondria, smooth ER, microtubules (move organelles and vesicles) and neurofilaments (structural backbone)

Answer 217

conductive region of the cell = conducts nervous impulses away from cell body towards axon terminal; has mitochondria and SER (but few/no ribosomes or RER; no protein synthesis), has many microtubules for the transport of vesicles and organelles up and down the axon

Answer 218

'end bulb'; portion of the axon that comes into close proximity with a target cell (another neuron, or muscle cell, or glandular cell) at a connecting 'synapse' where information is passed

Answer 219

* Site of neuron to neuron interactions (eg. axodendritic and axosomatic depending on location) * Modified at sites of neuron-to-muscle cell (i.e. the neuromuscular junction; see Lect 13) and neuron-to-gland cell interaction.

Answer 220

- presynaptic axon Terminal - synaptic Cleft - post Synaptic terminal

Answer 221

site of vesicle accumulation that, in response to a conductive action potential that travels down the axon, fuse with the plasma membrane (via SNARES) to release neurotransmitter by exocytosis into the...

Answer 222

intercellular/extracellular space between the two neurons that contains the released neurotransmitter during 'synaptic transmission' such that it can bind to the...

Answer 223

which has cell surface receptors to receive neurotransmitters that, when bound, initiate a receptive action potential in the neuron that receives the signal.