Classes- Cell Tissue Biology Flashcards

Question

Glycosaminoglycans (GAGs)

Answer 1

Hyaluronic acid, dermatan sulfate, chodroitin sulfate, heparin, heparatan sulfate, and keratan sulfate; -are long unbranched polysaccharides, highly negatively charged, containing a repeating disaccharide unit: N-acetylgalactosamine (GaINAc) or N-acetylglucosamine (GIcNAc), and a uronic acid such as glucuronate or iduronate. GAGs confer high viscosity to the solution and low compressibility, which makes these molecules ideal for a lubricating fluid in the joints. At the same time, their rigidity provides structural integrety to cells and provides passageways between cells, allowing for cell migration. Hyaluronic acid is unique among the GAGs in that it does not contain any sulfate and is not found covalently attached to proteins as a proteoglycan. It has very large molecular weight and can displace a large volume of water.

Answer 2

Are proteins linked to GAGs (also called mucopolysaccharides). - GAGs extend perpendiculary from the core in a brush-like structure. The linkage of GAGs to the protein core involves a specific trisaccharide which is linked to the protein core through an O-glycosidic bond to a S or T residue in the protein.

Answer 3

In their on state bind and regulate the activity of effector proteins.

Answer 4

1-Binding of hormone induces a conformational change in receptor 2-Activated receptor binds to Galfa subunit 3-Binding induces conformational change in Galfa; bound GDP dissociates and is replaced by GTP; Galfa dissociates from G(beta-gama) 4-Hormone dissociates from receptor; Galfa binds to effector, activating it 5-Hydrolysis of GTP to GDP causes Galfa to dissociate from effector and reassociate with G(beta-gama)

Answer 5

In the liver, glucagon and epinephrine bind to different receptors, but both receptors interact with and activate the same Gsa, which activates adenylyl cyclase, thereby triggering the same metabolic responses. Positive and negative regulation of adenylyl cyclase activity occurs in some cell types, providing fine-tuned control of the cAMP level. For example, stimulation of adipose cells by epinephrine, glucagon, or ACTH activates adenylyl cyclase, whereas prostaglandin* PGE1 or adenosine inhibits the enzyme.

Answer 6

cAMP-activated protein kinase A (PKA) mediates various responses in different cells - alters the transcription of specific genes or the activity of specific proteins- by phosphorylation of serine and threonine residues in the target proteins (X-R-(R/K)-X-(S/T)-F). At low concentrations of cAMP, the PKA is an inactive tetramer. Binding of cAMP to the regulatory (R) subunits causes a conformational change in these subunits that permits release of the active, monomeric catalytic (C) subunits. cAMP binding is cooperative.

Answer 7

Kinase cascade that transmits signals downstream from mating factor receptors in S. cerevisiae. The receptors for yeast a and a mating factors are coupled to the same trimeric G protein. Ligand binding leads to activation and dissociation of the G protein. In the yeast mating pathway, the dissociated Gbg activates a protein kinase cascade analogous to the cascade downstream of Ras that leads to activation of MAP kinase. The final component, Fus3, is functionally equivalent to MAP kinase (MAPK) in higher eukaryotes. Association of several kinases with the Ste5 scaffold contributes to specificity of the signaling pathway by preventing phosphorylation of other substrates.

Answer 8

Synthesis of DAG and IP3 (diffusible) from membrane-bound phosphstidylinositol (PI). The level of PIs are regulated by extracellular signals, especially those that bind to receptor tyrosine kinases or cytokine receptors.

Answer 9

This pathway can be triggered by ligand binding to certain G protein-coupled receptors and several other receptor types, leading to activation of phospholipase C. Cleavage of PIP2 by phospholipase C. Cleavage of PIP2 by phospholipase C yields IP3 interacts with opens Ca 2+ channels in the membrane of the endoplasmic reticulum, causing release of stored Ca 2+ ions into the cytosol. One of various cellular responses induced by a rise in cytosolic Ca2+ is recruitment of protein kinase C (PKC) to the plasma membrane, where it is activated by DAG. The activated Kinase can phosphorylate various cellular enzymes and receptors, thereby altering their activity. As endoplasmic reticulum Ca 2+ stores are depleted, the IP3-gated Ca2+ channels bind to and open store-operated TRP Ca2+ channels in the plasma membrane, allowing influx of extracellular Ca 2+.

Answer 10

The Ca2+/calmodulin complex regulates the activity of many different proteins (e.g. cAMP-phosphodiesterase, nitric oxide synthase) and kinases (e.g. GPK that hydrolyses glycogen) and phosphatases that control the activity of various proteins including transcription factors.

Answer 11

Nitric oxide (NO) is synthesized in endothelial cells in response to acetylcholine and the subsequent elevation in cytosolic Ca2+. NO diffuses to nearby smooth muscle cells where activates an intracellular NO receptor with guanylyl cyclase activity. The resulting rise in cGMP leads to activation of protein kinase G (PKG) (which indirectly induces dephosphorylation of myosin), relaxation of the muscle, and thus vasodilation. (Nitroglycerin (is converted to NO by mitochondrial aldehyde dehydrogenase) and “Viagra” inhibit a cGMP-phosphodiesterase)

Answer 12

The high level of cGMP present in the dark acts to keep cGMP-gated cation channels open; the light-induced decrease in cGMP leads to channel closing, membrane hyperpolarization (cell interior more negative), and reduced neurotransmitter release

Answer 13

In dark-adapted rod cells , a high level of cGMP keeps nucleotide-gated nonselective cation channels open. Light absorption generates activated opsin, O* , which binds inactive GDP-bound Gt protein and mediates replacement of GDP with GTP. The free Gt(alfa) GTP generated then activates cGMP phosphodiesterase (PDE) by binding to its inhibitory gama subunits and dissociating them from the catalytic alfa and beta subunits. Relieved of the inhibition, the alfa and beta subunits convert cGMP to GMP. The resulting decrease in cytosolic cGMP leads to dissociation of cGMP from the nucleotide-gated channels in the plasma membrane and closina of the channels. The membrane then becomes transiently hyperpolarized.

Answer 14

Operational model of muscarinic acetylcholine receptor in the heart muscle plasma membrane. The exit of K+ results in hyperpolarization of the cell membrane that slows the rate of muscle contraction.

Answer 15

- hydrolysis of GTP to GDP, which is accelerated by GAPs and RGSs, causes Gα to dissociate from effector and bind with Gßɣ - upon phosphorylation of the GPCR by protein kinases (PKs) or GPCR kinases (GRKs) arrestin binding may occur preventing G-protein coupling as well triggering the process of receptor internalization through clathrin-mediated endocytosis

Answer 16

Small lipophilic molecules like steroids (cortisol, progesterone, estradiol, testosterone), thyroxine and retinoic acid diffuse across plasma membrane and interact with intracellular receptors altering gene expression at transcription or post-transcription level. Long term stimulus (hours to days).

Answer 17

Arrival of an action potential at the terminus of a presynaptic motor neuron induces opening of voltage- gated Ca2+ channels (step 1) and subsequent release of acetylcholine, which triggers opening of the ligand-gated nicotinic receptors that are ion channels in the muscle plasma membrane (step 2). The resulting influx of Na+ produces a localized depolarization of the membrane, leading to opening of voltage-gated Na+ channels and generation of an action potential (step 3). When the spreading depolarization reaches T tubules, it triggers opening of voltage-gated Ca2+-release channels and release of Ca2+ from the sarcoplasmic reticulum into the cytosol (step 4). The rise in cytosolic Ca2+ causes muscle contraction

Answer 18

■ Stimulation by TGFb leads to activation of the intrinsic serine/threonine kinase activity in the cytosolic domain of the type I (RI) receptor, which then phosphorylates an R-Smad, exposing a nuclear-localization signal. ■ After phosphorylated R-Smad binds a co-Smad, the resulting complex translocates into the nucleus, where it interacts with various transcription factors to induce expression of target genes. ■ TGFb signaling generally inhibits cell proliferation. Loss of various components of the signaling pathway contributes to abnormal cell proliferation and malignancy.

Answer 19

- have serine/threonine kinase activity - directly activate Smads and then the transcription of PAI-1

Answer 20

Step 1a: In some cells, TGFb binds to the type III TGFb receptor (RIII), which presents it to the type II receptor (RII). Step 1b: In other cells, TGFb binds directly to RII, a constitutively phosphorylated and active kinase. Step 2: Ligand-bound RII recruits and phosphorylates the juxtamembrane segment of the type I receptor (RI), which does not directly bind TGFb. This releases the inhibition of RI kinase activity that otherwise is imposed by the segment of RI between the membrane and kinase domain. Step 3: Activated RI then phosphorylates Smad3 (shown here) or another R-Smad, causing a conformational change that unmasks its nuclear- localization signal (NLS). Step 4: Two phosphorylated molecules of Smad3 interact with a co- Smad (Smad4), which is not phosphorylated, and with importin b (Imp-b), forming a large cytosolic complex. Steps 5 and 6: After the entire complex translocates into the nucleus, RanGTP causes dissociation of Imp-b. Step 7: A nuclear transcription factor (e.g., TFE3) then associates with the Smad3/Smad4 complex, forming an activation complex that cooperatively binds in a precise geometry to regulatory sequences of a target gene. Shown at the bottom is the activation complex for the gene encoding plasminogen activator inhibitor (PAI-1).

Answer 21

is a protein that controls proliferation, cellular differentiation, and other functions in most cells

Answer 22

Receptor tyrosine kinases (RTKs), which bind to peptide and protein hormones, may exist as preformed dimers or dimerize during binding to ligands. Ligand binding leads to activation of the intrinsic protein tyrosine kinase activity of the receptor and phosphorylation of tyrosine residues in its cytosolic domain. The activated receptor also can phosphorylate other protein substrates. Ras is an intracellular GTPase switch protein that acts downstream from most RTKs. Like G protein, Ras cycles between an inactive GDP-bound form and an active GTP-bound form. Ras cycling requires the assistance of two proteins, a guanine nucleotide–exchange factor (GEF) and a GTPase-activating protein (GAP).

Answer 23

- share many signaling features - the phosphotyrosines of the receptors are docking sites for proteins (with SH2 domains)

Answer 24

The cytosolic domain of RTKs contains a protein tyrosine kinase catalytic site, whereas the cytosolic domain of cytokine receptors associates with a separate JAK kinase (step 1). In both types of receptor, ligand binding causes a conformational change that promotes formation of a functional dimeric receptor, bringing together two intrinsic or associated kinases, which then phosphorylate each other on a tyrosine residue in the activation lip (step 2). Phosphorylation causes the lip to move out of the kinase catalytic site, thus allowing ATP or a protein substrate to bind. The activated kinase then phosphorylates other tyrosine residues in the receptor’s cytosolic domain (step 3). The resulting phosphotyrosines function as docking sites for various signal- transduction proteins

Answer 25

The receptors for epidermal growth factor (EGF) and many other growth factors are RTKs. The cytosolic adapter protein GRB2 binds to a specific phosphotyrosine on an activated, ligand-bound receptor and to the cytosolic Sos protein, bringing it near its substrate, the inactive RasGDP. The guanine nucleotide–exchange factor (GEF) activity of Sos then promotes formation of active RasGTP. Note that Ras is tethered to the membrane by a hydrophobic farnesyl anchor

Answer 26

In unstimulated cells, most Ras is in the inactive form with bound GDP; binding of a ligand to its RTK or cytokine receptor leads to formation of the active RasGTP complex (step 1). Activated Ras triggers the downstream kinase cascade depicted in steps 2–6, culminating in activation of MAP kinase (MAPK). In unstimulated cells, binding of the 14-3-3 protein to Raf stabilizes it in an inactive conformation. Interaction of the Raf N-terminal regulatory domain with RasGTP relieves this inhibition, results in dephosphorylation of one of the serines that bind Raf to 14-3-3, and leads to activation of Raf kinase activity (steps 2 and 3). Note that in contrast to many other protein kinases, activation of Raf does not depend on phosphorylation of the activation lip. After inactive RasGDP dissociates from Raf, it presumably can be reactivated by signals from activated receptors, thereby recruiting additional Raf molecules to the membrane.

Answer 27

■ Erythropoietin, a cytokine secreted by kidney cells, prevents apoptosis and promotes proliferation and differentiation of erythroid progenitor cells in the bone marrow. An excess of erythropoietin or mutations in its receptor that prevent down-regulation result in production of elevated numbers of red blood cells. ■ All cytokine receptors are closely associated with a JAK protein tyrosine kinase, which can activate several downstream signaling pathways leading to changes in transcription of target genes or in the activity of proteins that do not regulate transcription. and several SOCS proteins. ■ The JAK-STAT pathway operates downstream of all cytokine receptors. STAT monomers bound to receptors are phosphorylated by receptor-associated JAKs, then dimerize and move to the nucleus, where they activate transcription.

Answer 28

Following ligand binding to a cytokine receptor and activation of an associated JAK kinase, JAK phosphorylates several tyrosine residues on the receptor’s cytosolic domain. After an inactive monomeric STAT transcription factor binds to a phosphotyrosine in the receptor, it is phosphorylated by active JAK. Phosphorylated STATs spontaneously dissociate from the receptor and spontaneously dimerize. Because the STAT homodimer has two phosphotyrosine–SH2 domain interactions, whereas the receptor-STAT complex is stabilized by only one such interaction, phosphorylated STATs tend not to rebind to the receptor. The STAT dimer, which has two exposed nuclear-localization signals (NLS), moves into the nucleus, where it can bind to promoter sequences and activate transcription of target genes.

Answer 29

■ Wnt pathway is involved in carcinogenesis and in embryonic development. The canonical pathway avoids β-catenin degradation that can be translocated into the nucleus promoting transcription of target genes. ■ Upon binding to its ligand Delta on the surface of an adjacent cell, the Notch receptor protein undergoes two proteolytic cleavages. The released Notch cytosolic segment then translocates into the nucleus and modulates gene transcription. ■ The NF-kB transcription factor regulates many genes that permit cells to respond to infection and inflammation. ■ In unstimulated cells, NF-kB is localized to the cytosol, bound to an inhibitor protein, I-kB. In response to extracellular signals, phosphorylation-dependent ubiquitination and degradation of I-kB in proteasomes releases active NF-kB, which translocates to the nucleus.

Answer 30

The canonical Wnt pathway leads to regulation of gene transcription, the noncanonical planar cell polarity pathway regulates the cytoskeleton that is responsible for the shape of the cell, and the noncanonical Wnt/calcium pathway regulates calcium inside the cell. Wnt signaling is involved in carcinogenesis and in embryonic development. (a) Canonical pathway, signaling through the Frizzled (Fz) and LRP5/6 receptor complex induces the stabilization of β-catenin via the DIX and PDZ domains of Dishevelled (Dsh) and a number of factors including Axin, glycogen synthase kinase 3 (GSK3) and casein kinase 1 (CK1). β-catenin translocates into the nucleus where it complexes with members of the LEF/TCF family of transcription factors to mediate transcriptional induction of target genes. β- catenin is then exported from the nucleus and degraded via the proteosomal machinery. (b) Non-canonical or planar cell polarity signaling is transduced via Frizzled independent of LPR5/6. Utilizing the PDZ and DEP domains of Dsh, this pathway mediates cytoskeletal changes through activation of the small GTPases Rho and Rac. (c) Wnt-Ca2+ pathway: Frizzled mediates activation of heterotrimeric G-proteins, which engage Dsh, phospholipase C (not shown), calcium-calmodulin kinase 2 (CamK2) and protein kinase C (PKC).

Answer 31

The extracellular subunit of Notch on the responding cell is non covalently associated with its transmembrane-cytosolic subunit. Binding of Notch to its ligand Delta on an adjacent signaling cell (step 1) first triggers cleavage of Notch by the membrane-bound metalloprotease TACE (tumor necrosis factor alpha converting enzyme), releasing the extracellular segment (step 2). Presenilin 1, an integral membrane protein, then catalyzes na intramembrane cleavage that releases the cytosolic segment of Notch (step 3). Following translocation to the nucleus, this Notch segment interacts with several transcription factors that act to affect expression of genes that in turn influence the determination of cell fate during development (step 4).

Answer 32

In resting cells, the dimeric transcription factor NF-kB, composed of p50 and p65, is sequestered in the cytosol, bound to the inhibitor I-kB. Stimulation by TNF-a or IL-1 induces activation of TAK1 kinase (step 1), leading to activation of the trimeric I-kB kinase (step 2a). Ionizing radiation and other stresses can directly activate I-kB kinase by an unknown mechanism (step 2b). Following phosphorylation of I-kB by I-kB kinase and binding of E3 ubiquitin ligase (step 3), polyubiquitination of I-kB (step 4) targets it for degradation by proteasomes (step 5). The removal of I-kB unmasks the nuclear-localization signals (NLS) in both subunits of NF-kB, allowing their translocation to the nucleus (step 6). Here NF-kB activates transcription of numerous target genes (step 7), including the gene encoding the subunit of I-kB, which acts to terminate signaling.

Answer 33

■ Insulin and glucagon work together to maintain a stable blood glucose level ■ A rise in blood glucose triggers insulin secretion from the 𝛃 islet cells ■ In fat and muscle cells, insulin triggers fusion of intracellular vesicles containing the GLUT4 glucose transporter to the plasma membrane ■ Insulin inhibits glucose synthesis and enhances storage of glucose as glycogen. Secretion of insulin in response to a rise in blood glucose. The entry of glucose into pancreatic β cells is mediated by the GLUT2 glucose transporter (step 1). The conversion of glucose into pyruvate is thus accelerated, resulting in an increase in the concentration of ATP in the cytosol (step 2). The binding of ATP to ATP-sensitive K+ channels in the β cells closes those channels (step 3), thus reducing the efflux of K+ ions from the cell. The resulting small depolarization of the plasma membrane (step 4) triggers the opening of voltage- sensitive Ca2+ channels (step 5). The influx of Ca2+ ions raises the cytosolic Ca2+ concentration, triggering the fusion of insulin-containing secretory vesicles with the plasma membrane and the secretion of insulin (step 6).

Answer 34

In the cytosol, MAP kinase phosphorylates and activates the kinase p90RSK, which then moves into the nucleus and phosphorylates the SRF transcription factor. After translocating into the nucleus, MAP kinase directly phosphorylates the transcription factor TCF. Together, these phosphorylation events stimulate transcription of genes (e.g., c-fos) that contain an SRE sequence in their promoter. MAP kinase pathways that are triggered by activation of various receptor classes including GPCRs

Answer 35

(a) SHP1, a protein tyrosine phosphatase, is present in an inactive form in unstimulated cells. Binding of an SH2 domain in SHP1 to a particular phosphotyrosine in the activated receptor unmasks its phosphatase catalytic site and positions it near the phosphorylated tyrosine in the lip region of JAK2. Removal of the phosphate from this tyrosine inactivates the JAK kinase. (b) SOCS proteins, whose expression is induced in erythropoietin-stimulated erythroid cells, inhibit or permanently terminate signaling over longer time periods. Binding of SOCS to phosphotyrosine residues on the EpoR or JAK2 blocks binding of other signaling proteins (left). The SOCS box can also target proteins such as JAK2 for degradation by the ubiquitin proteasome pathway (right). Similar mechanisms regulate signaling from other cytokine receptors.

Answer 36

Two phosphoinositide pathways are triggered by recruitment of phospholipase C and PI-3 kinase to the membrane following activation of EpoR. Elevated levels of Ca2+ and activated protein kinase B also modulate the activity of cytosolic proteins that are not involved in control of transcription.

Answer 37

Antibodies targeting IL-R6 (e.g. Tocilizumab, Sarilumab) or TNFa (Adalimumab)

Answer 38

Insulin stimulation of fat cells induces translocation of GLUT4 from intracellular vesicles to the plasma membrane. In fat and muscle cells, insulin signaling acts in multiple steps to increase the level of GLUT4 at the plasma membrane. In resting cells, the majority of the GLUT4 protein is localized to specialized GLUT4 storage vesicles, tethered to Golgi matrix proteins by the TUG protein. Binding of insulin to the insulin receptor leads to activation of a protease (step 1) that cleaves the TUG protein, releasing GLUT4-containing vesicles (step 2), which then move along microtubules, powered by a kinesin motor, to the cell surface. Insulin also activates PKB (step 3). PKB then phosphorylates the Rab GAP protein AS160 (step 4), inhibiting its ability to accelerate GTP hydrolysis by Rab proteins, which accumulate in their active GTP-bound states (step 5) and allow the GLUT4 storage vesicles to move along microtubules to the cell surface (steps 6a and 6b). Finally, these vesicles fuse with the plasma membrane (step 7). This step is catalyzed by the exocyst and also by another monomeric GTP-binding protein, RALA. PKB stimulates this membrane fusion event by phosphorylating and thus inactivating the RALA GAP protein RGC (step 8), allowing RALA to accumulate in its active GTP-bound state (step 9). The resultant increase in plasma membrane GLUT4 allows the cell to incorporate glucose from the extracellular fluids at a rate about 10 times that of unstimulated cells (step 10). Following removal of insulin, the plasma membrane GLUT4 is internalized by endocytosis (step 11) and eventually transported to vesicles (step 12). Many other proteins, not shown here, participate in these signaling and vesicle budding and fusion events.

Answer 39

Active enzymes are highlighted in darker shades; inactive forms, in lighter shades. (a) An increase in cytosolic cAMP activates PKA, which inhibits glycogen synthesis directly and promotes glycogen degradation via a protein kinase cascade. At high cAMP, PKA also phosphorylates an inhibitor of phosphoprotein phosphatase (PP). Binding of the phosphorylated inhibitor to PP prevents this phosphatase from dephosphorylating the activated enzymes in the kinase cascade or the inactive glycogen synthase. (b) A decrease in cAMP inactivates PKA, leading to release of the active form of phosphoprotein phosphatase. The action of this enzyme promotes glycogen synthesis and inhibits glycogen degradation.

Answer 40

- Interruption or suppression of the expression of a gene at transcriptional (=epigenetics*) or post-transcriptional levels - When genes are silenced or knockdown, their expression is reduced or even abolished (is often confused with gene knockout)

Answer 41

- is the result of histone modifications (methylation, acetylation, phosphorylation, ubiquitylation, and sumoylation) and DNA methylation, creating an environment of heterochromatin around a gene that makes it inaccessible to transcriptional machinery. - DNA methylation of a gene promoter typically acts to repress its transcription - Histone modifications act in transcriptional activation/inactivation

Answer 42

is the result of degradation of a specific mRNA preventing its translation. A usual mechanism of post-transcriptional gene silencing is RNAi.

Answer 43

dsRNA (either transcribed or artificially introduced) is processed by Dicer into siRNA which is loaded into the RISC. AGO2, which is a component of RISC, cleaves the passenger strand of siRNA. The guide strand then guides the active RISC to the target mRNA. The full complementary binding between the guide strand of siRNA and the target mRNA leads to the cleavage of mRNA.

Answer 44

Transcription of miRNA gene is carried out by RNA polymerase II in the nucleus to give pri-miRNA, which is then cleaved by Drosha to form pre-miRNA. The pre-miRNA is transported by Exportin 5 to the cytoplasm where it is processed by Dicer into miRNA. The miRNA is loaded into the RISC where the passenger strand is discarded, and the miRISC is guided by the remaining guide strand to the target mRNA through partially complementary binding. The target mRNA is inhibited via translational repression, degradation or cleavage.

Answer 45

The recent discovery of reversible mRNA methylation has opened a new realm of post-transcriptional gene regulation in eukaryotes. The identification and functional characterization of proteins that specifically recognize RNA m6A (N6-methyladenosine) unveiled it as a modification that cells utilize to accelerate mRNA metabolism (processing in the nucleus to translation and decay in cytoplasm) and translation

Answer 46

A tissue is a collection of cells and ECM that perform a given function. Organs are composed of parenchyma, made up by cells responsible for the function of the organ and stroma which is the supporting tissue

Answer 47

-Usually grow in contiguous 2D sheets -Tightly connected with their neighbors (cannot migrate) -They have polarity -They are bound to a basal lamina

Answer 48

-Usually exist alone -Have a bipolar shape -They can migrate -Their growth is contact-inhibited -They can differentiate into osteoblasts, chondrocytes, fibroblasts

Answer 49

Epithelial tissues are composed of closely aggregated polyhedral cells with very little extracellular substance but showing strong adherence to each other (tight junctions, desmosomes, adherens junctions, gap junctions). Are not irrigated by blood vessels.

Answer 50

Covering and lining of surfaces (e.g. skin, intestines), absorption (e.g. intestines), secretion (e.g. glands), sensation (e.g. olfactory neuroepithelium) Epithelia classification is based on: - Number of cell layers: simple (one sheet) or stratified (multilayered) - Cell (and also nucleus) shape: squamous (“pavimentoso”) (flattened), cuboid, columnar or pseudostratified (has only one cell layer but looks like more) - Presence of cell surface specializations (Microvilli that increase the cell surface area; and Cilia that allows a current of fluid to be propelled in one direction)

Answer 51

Section of a vein containing red blood cells. All blood vessels are lined with a simple squamous epithelium called endothelium (arrowheads)

Answer 52

The simple squamous epithelium that covers the body cavities (the abdominal cavity in this case) is called mesothelium

Answer 53

Connective tissues are composed mainly of ECM (unlike other tissues). The wide variety reflects variations in the composition and amount of cells and ECM. Are originated from the mesenchyme (an embryonic tissue) that develops from mesoderm. Main functions: Provide and maintain form in the body, and structural and metabolic aid for other tissues

Answer 54

are derived from B lymphocytes and produces antibodies

Answer 55

is rich in adipocytes which are also found isolated or in small groups in other connective tissues is highly vascularized. It is the largest organ in the body... (in men 15-20% and in women 20-25% of body weight)

Answer 56

is characterized by chondrocytes and an ECM enriched with GAGs and proteoglycans. Variations in the ECM composition originate hyaline, elastic and fibrous cartilages.

Answer 57

supports fleshy structures, protects vital organs (cranial and thoracic cavities) and harbours the bone marrow where blood is formed. Is highly vascularized and metabolically active. It serves as a reservoir of ions (calcium, phosphate, etc). Has a mineralized ECM and inside lacunae, osteocytes/osteoblasts which synthesize the organic ECM, and osteoclasts which make reabsorption and remodeling of the bone tissue.

Answer 58

Lysosomal enzymes packaged in the Golgi complex and protons are released into the bone matrix. The acidification facilitates the dissolution of calcium phosphate from bone and is the optimal pH for the activity of lysosomal hydrolases (e.g. collagenases). Bone matrix is thus removed and the products of bone resorption are taken up by the osteoclast’s cytoplasm, probably digested further, and transferred to blood capillaries.

Answer 59

is found in the hollow interior of bones. It constitutes 4% of total body weight, and is responsible for hematopoiesis (erythropoiesis, granulonopoiesis, monocytopoiesis, megacaryocytopoiesis or thrombopoiesis). - Network of stromal cells (fibroblasts, macrophages, adipocytes, osteoblasts, osteoclasts, endothelial cells forming the sinusoids) and hematopoietic cells - Produces 2.5x109 erythrocytes and 2.5x109 platelets and 50-100x109 granulocytes per day and per kg of body weight! - Removes (like liver and spleen) damaged erythrocytes - Is the place for B lymphocytes maturation. A femur showing its red bone marrow and a focus of yellow bone marrow consisting mainly of fat cells (progressively substitutes red marrow in adults)

Answer 60

Circulating lymphocytes originate (lymphopoiesis) mainly in the thymus and the peripheral lymphoid organs (spleen, lymph nodes, tonsils). Some migrate to thymus where they become T-lymphocytes and other differentiate at bone marrow, B-lymphocytes. The lymphoid organs and lymphatic vessels are widely distributed in the body. The lymphatic vessels collect lymph from most parts of the body and deliver it to the blood circulation primarily through the thoracic duct.

Answer 61

Cardiac muscle is composed of irregular branched cells bound together longitudinally by intercalated disks. Smooth muscle is an agglomerate of fusiform cells. Skeletal muscle is composed of large, elongated, multinucleated fibers.

Answer 62

Arrival of an action potential at the terminus of a presynaptic motor neuron induces opening of voltage-gated Ca2+ channels (step 1) and subsequent release of acetylcholine, which triggers opening of the ligand-gated nicotinic receptors in the muscle plasma membrane (step 2). The resulting influx of Na+ produces a localized depolarization of the membrane, leading to opening of voltage-gated Na+ channels and generation of an action potential (step 3). When the spreading depolarization reaches T tubules, it triggers opening of voltage-gated Ca2+ channels and release of Ca2+ from the sarcoplasmic reticulum into the cytosol (step 4). The rise in cytosolic Ca2+ causes muscle contraction.

Answer 63

Muscle contraction, initiated by the binding of Ca2+ to the TnC unit of troponin, which exposes the myosin binding site on actin (cross-hatched area). In a second step, the myosin head binds to actin and the ATP is hydrolysed yielding energy, which produces a movement of the myosin head. As a consequence of this change in myosin, the bound thin filaments slide over the thick filaments reducing the distance between the Z lines, thereby shortening of the whole muscle fiber.

Answer 64

Nerve tissue is composed of nerve cells (neurons) which sense, process and respond to features of both internal and external environment, glial cells (neuroglia) which occupy space between neurons and modulate their functions. Each neuron has many interconnections with other neurons.

Answer 65

Neurons are responsible for the reception, transmission, and processing of stimuli, the triggering of certain cell activities, and release of neurotransmitters. Generally, receive information via their dendrites and transmit information via their axons to other neurons or other cells forming synapses. Where neurons and their target cells meet, information is transmitted across synapses by the release of neurotransmitters.

Answer 66

Neurons have an electric charge difference across their plasma membranes. The difference in voltage across membrane is called membrane potential. In an unstimulated neuron is called resting potential. Nerve impulses are also called action potentials and travel along the plasma membrane. - The negative resting potential is created by the 3Na+/2K+ ATPase and K+ and Na+ ion channels. - Na+- K+ pump moves 2 K+ ions inside the cell as 3 Na+ ions are pumped out. - K+ ions diffuse out of the cell at a faster rate than Na+ ions diffuse into the cell because neurons have more K+ leakage channels than Na+ leakage channels.

Answer 67

An action potential is a rapid reversal in charge across a portion of the plasma membrane resulting from the sequential opening and closing of voltage-gated sodium and potassium channels. These changes in voltage-gated channels occur when the plasma membrane depolarizes to a threshold level.

Answer 68

Synapses are functional connections for communication between neurons or neurons and other cells. Synaptic transmission begins with the arrival of an action potential Synapses can be excitatory or inhibitory (the neuromuscular is always excitatory)

Answer 69

SNAREs can be divided into two categories: vesicle or v-SNAREs, which are incorporated into the membranes of transport vesicles during budding, and target or t- SNAREs, which are associated with nerve terminal membranes.

Answer 70

- Some protein degradation pathways are nonspecific. But there is also a selective, ATP-dependent pathway for degradation - the ubiquitin-mediated pathway

Answer 71

Epigenetic drugs make it possible to reverse the aberrant gene expression which leads to various disease states. The inhibitors, DNA methyltransferase (DNMT) and Histone Deacetylase (HDAC) are responsible for regulating the cellular expression. Currently, several drugs are approved by FDA and are commercially available. Slide 160

Answer 72

BMP (TGFß superfamily) and Wnt signaling pathways have been demonstrated to preferentially induce the osteogenesis of MSCs at the expense of adipogenesis. miR-17-5p/miR-106a and miR-30c/miR-30d inhibit BMP signaling by targeting key components of the pathway, such as BMP2 and Smad1, respectively. miR-30e inhibits Wnt signaling via the repression of LPR6, a key co-receptor of Wnt.

Answer 73

supports many structures that are normally under pressure and low friction. It is flexible, well vascularized and not very resistant to stress e.g. between muscle cells, supports epithelial tissue and forms a layer that sheathes the lymphatic and blood vessels.

Answer 74

Have fewer cells than loose connective tissue and a clear predominance of collagen fibers. There are 2 types: irregular and regular dense connective tissues.

Answer 75

Triglycerides are transported in blood from the intestine and liver by lipoproteins known as chylomicrons and VLDLs. In adipose tissue capillaries, these lipoproteins are partly broken down by lipoprotein lipase, releasing fatty acids. The free fatty acids diffuse from the capillary into the adipocyte, where they are re-esterified to glycerol phosphate, forming triglycerides. These resulting triglycerides are stored in droplets until needed. Norepinephrine from nerve endings stimulates the cAMP system, which activates hormone-sensitive lipase. Hormone-sensitive lipase hydrolyzes stored triglycerides to free fatty acids and glycerol. These substances diffuse into the capillary, where free fatty acids are bound to the hydrophobic moiety of albumin for transport to distant sites for use as an energy source.

Answer 76

- Some tissues produce cells (bone marrow, skin) as their main function, while others produce a secreted product (glands). Some tissues primarily carry out mass-transfer operations (lungs, kidneys) while others are biochemical “refineries” (liver) or can adapt to physiological need (hypertrophy of muscle).

Answer 77

wounded tissue displays a healing process that is relevant to tissue engineering - A biopsied piece or a graft of tissue is expected to initially display a healing -type response after being placed in culture or engrafted. Tissue repair occurs in phases: Early in the process (days), there is a coordination between cell proliferation, adhesion and migration. Remodeling of the wound occurs later (weeks to years) as a result of cell differentiation and ECM proper formation. The healing response is faster in fetus and slower in adults

Answer 78

the formation of tissue involves developmental biology including morphogenesis (describes the evolution and development of form). Morphological changes are important in the formation and subsequent function of the tissue and are fundamental to tissue formation and repair.

Answer 79

is a process by which a cell undergoes phenotypic changes to a defined specialized type (is the process where a cell changes from one cell type to another). After fertilization of an egg, several cell divisions and differentiation take place. This spherical mass reorganizes forming blastocyst containing a cavity, and starting gastrulation which is a large-scale morphogenic process.

Answer 80

Epithelial–mesenchymal transition (EMT) is a cellular program crucial for embryogenesis, wound healing and malignant progression. During EMT, cell–cell and cell–ECM interactions are remodeled, which leads to the detachment of epithelial cells from each other and the underlying basal lamina, and a new transcriptional program is activated to promote the mesenchymal fate.

Answer 81

Several cell-intrinsic signaling pathways cooperate to induce the expression of epithelial–mesenchymal transition (EMT)-inducing transcription factors (ZEB, SNAIL and TWIST) that act pleiotropically to induce the transition to the mesenchymal or partially mesenchymal cell state.

Answer 82

Microbes and cells from multicellular organisms have similar metabolic phenotypes under similar environmental conditions. Unicellular organisms undergoing exponential growth often grow by fermentation of glucose into a small organic molecule such as ethanol. These organisms, and proliferating cells in a multicellular organism, both metabolize glucose primarily through glycolysis, excreting large amounts of carbon in the form of ethanol, lactate, or another organic acid such as acetate or butyrate. Unicellular organisms starved of nutrients rely primarily on oxidative metabolism, as do cells in a multicellular organism that are not stimulated to proliferate. This evolutionary conservation suggests that there is an advantage to oxidative metabolism during nutrient limitation and nonoxidative metabolism during cell proliferation.

Answer 83

In the presence of oxygen, nonproliferating (differentiated) tissues first metabolize glucose to pyruvate via glycolysis and then completely oxidize most of that pyruvate in the mitochondria to CO2 during the process of oxidative phosphorylation. Because oxygen is required as the final electron acceptor to completely oxidize the glucose, oxygen is essential for this process. When oxygen is limiting, cells can redirect the pyruvate generated by glycolysis away from mitochondrial oxidative phosphorylation by generating lactate (anaerobic glycolysis). This generation of lactate during anaerobic glycolysis allows glycolysis to continue (by cycling NADH back to NAD+), but results in minimal ATP production when compared with oxidative phosphorylation. Warburg observed that cancer cells tend to convert most glucose to lactate regardless of whether oxygen is present (aerobic glycolysis). This property is shared by normal proliferative tissues. Mitochondria remain functional and some oxidative phosphorylation continues in both cancer cells and normal proliferating cells. Nevertheless, aerobic glycolysis is less efficient than oxidative phosphorylation for generating ATP. In proliferating cells, ~10% of the glucose is diverted into biosynthetic pathways upstream of pyruvate production.

Answer 84

Mechanical loads can induce signal transduction by directly transmitting forces from the ECM to integrins, the cytoskeleton, and the nucleus, eventually resulting in changes in gene transcription and protein translation. Also, mechanical stretching of cells opens stretching- activated channels (SACs), causing influx of ions (e.g., Ca+) and thus a series of downstream signaling events. Still, mechanical loads acting on a cell may unfold a domain of the extracellular protein (M) and expose a cryptic site that may serve as an activating ligand for a cell surface receptor, which results in a series of signaling events. Additionally, mechanical load applied to a “force receptor” (FR) may initiate signal transduction, which results in transcription, followed by translation. As a result, soluble factors are secreted into the ECM which act on the receptor (R) and then initiate a cascade of signaling events. Other signaling molecules that are involved in mechanotransduction can include CD44 transmembrane protein and its intracellular domain (CD44ICD), which is translocated into the nucleus causing gene transcription.

Answer 85

1 Trachea is removed from dead donor patient 2 It is flushed with chemicals to remove all existing cells 3 Donor trachea "scaffold" coated with stem cells from the patient's hip bone marrow. Cells from the airway lining added 4 Once cells have grown (after about four days) donor trachea is inserted into patient's bronchus

Answer 86

In the context of nonneoplastic cells, the transforming growth factor-β (TGFβ), WNT and NOTCH pathways are activated during embryonic development and wound healing. Activation of EMT downstream of these pathways is crucial for palatal fusion and formation of the primitive streak , mesoderm and node in developing embryos. Additionally , TGFβ and WNT-induced EMT promotes wound healing and fibrosis. The canonical WNT pathway is activated upon binding of canonical WNT ligands to the Frizzled family of membrane receptors. This leads to the release of β-catenin from the GSK3β (glycogen synthase kinase-3β)–AXIN (axis inhibition protein)–APC (adenomatous polyposis coli protein) complex. β-Catenin then translocates to the nucleus, where it binds to the transcription factors TCF (T cell factor) and LEF (lymphoid enhancer-binding factor) to activate genes that drive EMT. The NOTCH pathway is activated upon binding of the Delta-like or Jagged family of ligands to the NOTCH receptor. This binding triggers a series of proteolytic cleavage events that culminate in the release of the active, intracellular domain of the NOTCH receptor (NOTCH-ICD), which enters the nucleus to function as a transcriptional co-activator. Binding of the TGFβ proteins to the TGFβ family of receptors leads to receptor phosphorylation and activation of SMAD complexes, which activate the EMT programme. SMAD proteins also interact with β-catenin and NOTCH-ICD (dashed arrows), serving as central nodes for crosstalk between the TGFβ, WNT and NOTCH pathways. The TGFβ pathway also collaborates with the PI3K AKT pathway, which in turn triggers the activation of the mTOR complex and nuclear factor-κB (NF- κB), the p38 MAPK pathway and the RAS–RAF–MEK–ERK signalling axis. The aforementioned pathways are also triggered upon binding of growth factors to their cognate receptors. Moreover, binding of several cytokines to their receptors triggers the phosphorylation and activation of Janus kinases (JAKs) and signal transducer and activator of transcription proteins (STATs); STAT dimers activate the transcription of genes encoding EMT transcription factors.

Answer 87

DNA demethylation of the zygote, gauged by 5mC levels, occurs by a passive mechanism in the female pronucleus, diluting the marks with the passage of every cell cycle. The male pronuclear genome becomes demethylated actively by the action of the Tet enzymes. Tet3 is expressed in the oocyte and zygote. After fertilization, Tet3 is relocated from the cytoplasm to the paternal nucleus to convert 5mC to 5hmC/5fC/5caC. Subsequently, paternal and maternal genomes undergo replication-dependent dilution of 5hmC/5fC/5caC in males and 5mCin females. It is possible that replication-independent active DNA demethylation may occur in a loci-specific manner in zygotes, but the exact mechanism is currently unclear. DNA methylation patterns in ICM are reestablished by de novo DNA methyltransferases DNMT3a and DNMT3b at the blastocyst stage.

Answer 88

Schematic representation of the composition and membrane orientation of EVs. Examples of tetraspanins commonly found in EVs include CD63, CD81, and CD9. Note that each listed component may in fact be present in some subtypes of EVs and not in others. For instance, histones and proteasome and ribosome components are probably secreted in large plasma membrane–derived EVs and/or apoptotic vesicles rather than exosomes. Abbreviations: ARF, ADP ribosylation factor; ESCRT, endosomal sorting complex required for transport; LAMP, lysosome-associated membrane protein; MHC, major histocompatibility complex; MFGE8, milk fat globule epidermal growth factor-factor VIII; RAB, Ras- related proteins in brain; TfR, transferrin receptor.

Answer 89

Via AKT, PI3K activation stimulates glucose uptake and flux through the early part of glycolysis. Tyrosine kinase signaling negatively regulates flux through the late steps of glycolysis, making glycolytic intermediates available for macromolecular synthesis as well as supporting NADPH production. Myc drives glutamine metabolism, which also supports NADPH production. LKB1/AMPK signaling and p53 decrease metabolic flux through glycolysis in response to cell stress. Decreased glycolytic flux in response to LKB/AMPK or p53 may be an adaptive response to shut off proliferative metabolism during periods of low energy availability or oxidative stress. Tumor suppressors are shown in red, and oncogenes are in green. Key metabolic pathways are labeled in purple with white boxes, and the enzymes controlling critical steps in these pathways are shown in blue. Some of these enzymes are candidates as novel therapeutic targets in cancer. Malic enzyme refers to NADP+-specific malate dehydrogenase [systematic name (S)-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating)].

Answer 90

In stem cells, pluripotent and housekeeping genes are actively transcribed within the nuclear interior while lineage-specific genes are silenced at the nuclear periphery. With lineage commitment, lineage-specific genes are detached from the nuclear lamina and relocated to the nuclear interior. In contrast, pluripotent genes are silenced and attach to the nuclear lamina. Additionally, some lineage-specific genes remain inactive despite being displaced from the nuclear envelope and are transcribed only after terminal differentiation.

Classes- Cell Tissue Biology Flashcards

(127 cards)