14/15/16 Flashcards
Extracellular Matrix
Provides structural support to cells and tissues and plays important roles in regulating cell behaviour
Cell Wall
Determines cell shape and prevents cells from swelling/bursting as a result of osmotic pressure
Bacterial Cell Wall Shapes
Rod, spherical, spiral
Gram Negative Bacteria
Dual-membrane system with thin cell wall in between
Gram Positive Bacteria
One plasma membrane surrounded by a much thicker cell wall
Peptidoglycan
Main component of all bacterial cell walls, linear polysaccharide chains cross-linked by short peptides
Cell Wall and Antibiotics
Cell wall structure makes some bacteria vulnerable to some antibiotics
Penicillin
Inhibits the enzyme that forms the cross-links in the cell wall, preventing growth and synthesis
Bacterial Cytoskeletal Proteins
Regulate cell wall synthesis
FtsZ
Cytoskeletal protein that forms a ring structure at the site of bacterial cell division and directs synthesis of a new cell wall
What are cell walls of eukaryotes composed of?
Polysaccharides
Chitin
Forms fungal cell walls and exoskeletons of arthropods
Cell Walls of Algae and Higher Plants
Cellulose
Hemicelluloses
Highly branched polysaccharides H-bonded to the surface of cellulose microfibrils. Provide stability and mechanical strength.
Pectins
Branched polysaccharides with many negatively charged galacturonic acids. Cross-link microfibrils, negative charges bind positive ions to trap water molecules and form gels.
Microfibrils
36 cellulose chains joined in parallel, can extend for many micrometers in length, embedded in a matrix of proteins/pectins/hemicelluloses
Primary Cell Walls
Relatively thin and flexible to allow expansion of a growing cell, equal amounts of cellulose/hemicelluloses/pectins, randomly arranged cellulose fibres
Secondary Cell Walls
Laid down between plasma membrane and primary cell wall after cell wall growth has stopped, no pectins, 50-80% cellulose, highly ordered layers with a strong laminated structure
Lignin
Complex polymer of phenolic residues that gives strength and density to wood
Turgor Pressure/Hydrostatic Pressure
Water builds up in cell, eventually equalizing the osmotic pressure and preventing further influx of water, responsible for the rigidity of plant tissues
Auxins
Plant hormones that activate expansins to allow expansion
Expansins
Proteins that weaken regions of the call wall to allow expansion
Water and the Vacuole
Water flows into the cell and accumulates in a large central vacuole so the cell can expand without increasing the volume of the cytosol
Cellulose Synthase
Trans-membrane enzyme that synthesizes cellulose from UDP-glucose
Microtubules
Guide movement of cellulose synthase and define orientation of newly synthesized microfibrils
Cortical Microtubules
Define the direction of cell wall growth and expansion and ultimately the shape of the entire plant
CLASP
Binds the + end of microtubules to regulate stability. Mutations that inactivate CLAPS results in stunted plants.
Basal Laminae
Thin layers that epithelial cells rest on. Also surrounds muscle cells, adipose cells, and peripheral nerves.
Extracellular Matrix
Embeds most animal cells, most abundant in CT, tough and fibrous proteins embedded in a gel-like polysaccharide
Adhesion Proteins
Link components of the matrix to one another and to attached cells
Tendon EM
High proportion of fibrous proteins
Cartilage EM
High level of polysaccharides that form a compression-resistant gel
Bone EM
Hardened by calcium phosphate crystals
Collagen
Major structural protein of EM, forms triple helices or repeat aa sequence Gly-X-Y
Glycine
Smallest amino acid, allows polypeptides to pack closely together in collagen
Proline
Frequently found in X position in collagen, stabilize helices
Hydroxyproline
Y position in collagen, stabilize helices, formed in ER by modification of proline in collagen polypeptide chains
Hydroxyl Groups in Collagen
Stabilize triple helix by forming H-bonds
Type I Collagen
Most abundant, forms collagen fibrils
Collagen Fibrils
Triple helical molecules form regular staggered arrays in them, strengthened by cross-links of lysine and hydroxylysine side chains, come together to form collagen fibres
Procollagens
Aid in assembly of fibrils outside the cell
Fibril-Associated Collagens
Bind to collagen fibrils and link them to one another and to other matrix components
Type IV Collagen
Mostly basal laminae, forms networks, Gly-X-Y repeats interrupted by short non-helical sequences to make them more flexible
Anchoring Fibrils
Link some basal laminae to underlying CTs
Elastic Fibres
Common in CT of organs that stretch and return to shape, made of elastin
Elastin
Cross-linked into a network to make elastic fibres, behaves like a rubber band
GAGs
Glycosaminoglycans, repeating units of disaccharides, form EM gels, highly negative because of sulphate groups, bind positive ions and trap water molecules to form hydrated gels, linked to proteins to form proteoglycans
Hyaluronan
Only GAG that is a single long polypeptide chain, synthesized at plasma membrane by a transmembrane hyaluronan synthase
Proteoglycans
GAGs linked to proteins, interact with hyaluronan to form large complexes in the extracellular matrix
Aggrecan
Major proteoglycan of cartilage, about 100 chains of chondroitin sulfate attached to a core protein
Fibronectin
Main adhesion protein of CT, often cross-linked into fibrils, binding sites for both collagen and GAGs to enable cross-linking
Laminin
Adhesion proteins in basal laminae, 3 ppc with rod-like domains and interspersed globular domains, subunits have binding sites for surface receptors and proteoglycans, can self-assemble into networks
Nidogen
Adhesion protein that also binds type IV collagen, tightly associated with laminins
Integrins
Transmembrane proteins that attach cells to the EM, heterodimers, bind to various components of the EM, anchor cytoskeleton to EM, can reversibly bind matrix components
Integrins as Heterodimers
Different combinations of subunits result in 24 different integrins
Types of Cell-Matrix Junctions
Focal adhesions and hemidesmosomes
Focal Adhesions
Bundles of actin filaments anchored to β subunits of integrins via other proteins, can be very stable or turn over rapidly as cells move
Hemidesmisomes
Anchor epithelial cells to basal laminae
How do integrins reversibly bind matrix components?
Due to their ability to change conformation between active and inactive states
How do animal cells modify their EM?
Via enzymes that modify glycosaminoglycans and proteases that digest collagen
Metalloproteases
Digest a variety of matrix proteins, play important roles in normal movements of cells during development and in the growth and metastasis of cancers
First Metalloprtease
Discovered in tadpole tails during metamorphosis
Cell Adhesion Molecules
Mediate cell-cell adhesion, selectins/integrins/immunoglobin superfamily/cadherins
Selectins
Mediate transient interactions between leukocytes and endothelial cells or blood platelets, bind to oligosaccharide ligands on endothelial cells
Heterophilic Interaction
An adhesion molecule on one cell recognizes a different molecule on another cell (ex: binding of ICAMs to integrins)
ICAMs
Intercellular adhesion molecules, members of the immunoglobin superfamily
Homophilic Interactions
An adhesion molecule on one cell binds to the same molecule on another cell (ex: binding between N-CAMs)
N-CAMs
Neural cell adhesion molecules, homophilic binding contributes to associations between nerve cells during development
Cadherins
Mediate homophilic interactions, basis of stable adhesion junctions linking the cytoskeletons of adjacent cells
Adherens Junctions
Link actin filaments of adjacent cells
Nectin
Can form homophilic and heterophilic interactions, present at adherent junctions, form links to the actin cytoskeleton
Desmosomes
Link intermediate filament cytoskeletons of adjacent cells
Tight Junctions in Epithelial Cell Sheets
Form a seal that prevents free passage of molecules and ions between cells, separate apical and basolateral domains of the plasma membrane by preventing free diffusion of lipids and membrane proteins, provide minimal adhesive strength between cells, formed by a network of protein strands that continues around the entire cell
Gap Junctions
Regulated channels through the plasma membrane, allow ions and small molecules to diffuse freely
Connexon
6 connexins, a cylinder with an open aqueous pore in its center, align between adjacent cells to form open channels between the two cytoplasms
Electrical Synapse
Specialized gap junctions on nerve cells, allow rapid passage of ions between 2 nerve cells
Middle Lamella
Pectin-rich region, acts as glue to hold adjacent cells together
Plasmodesmata
Analogous gap junctions for adjacent plant cells to communicate through cytoplasmic connections, form by incomplete separation of daughter cells following mitosis, plasma membrane of one cell is continuous with that of its neighbour to create a channel between the two cytosols, open and close to regulate passage
Plasma Membrane
Defines cell boundary and separates it from the environment, selective barrier that determines composition of the cytoplasm, mediates interactions between cell and environment
Bilayer in Electron Micrographs
Polar heads appear as dark lines because they bind the electron-dense metal stains, fatty acid tails are lightly stained
Mammalian Red Blood Cells and Membrane Structure
Useful model for studies, no nuclei or internal membranes so easy to isolate pure plasma membranes
Glycolipids
Only in outer leaflet of bilayer with carbohydrate portions exposed on the cell surface
Double Bonds in Fatty Acids of the Membrane
Make kinks in the chain and keep them from packing together
Cholesterol
Affects membrane fluidity and is involved in formation of functional domains in the membrane, clusters in small semisolid patches (lipid rafts)
% Weight of Plasma Membrane
50% lipid and 50% protein but proteins are much larger
Integral Membrane Proteins
Inserted into the lipid bilayer, dissociate only by reagents that disrupt hydrophobic interactions
Detergents
Amphipathic molecules with hydrophobic and hydrophilic groups that can solubilize integral membrane proteins
Transmembrane Proteins
Integral membranes that span the lipid bilayer with portions exposed on both side
GPI Anchors
Added to C terminus of some proteins in the ER, glycosylated and exposed on the cell surface
Glycocalyx
Carbohydrate coat formed by the oligosaccharides of glycolipids and glycoproteins, protects cell surface from ionic and mechanical stress, forms a barrier to invading microorganisms
Amendments to the Fluid Mosaic Model
Mobility of many plasma membrane proteins is restricted, membranes are composed of distinct domains that have different structural and functional roles
Domains of Plasma Membranes
Apical and basolateral
Apical Surface of SI
Covered in microvilli that increase surface area for absorption
Basolateral Surface of SI
Mediates transfer of absorbed nutrients to the blood
Separation of Apical and Basolateral Domains
Proteins must be restricted to their appropriate domains to maintain functions, tight junctions separate the domains, membrane proteins can move within each but can’t cross over
Lipid Rafts
Transient structures in which specific proteins can be concentrated to facilitate interactions
Caveolae
Small lipid rafts that start as invaginations of the plasma membrane
Facilitated Diffusion
Direction of movement determined by concentration gradients, no energy required
Carrier Proteins
Bind molecules on one side of the membrane then undergo conformational changes that allow the molecule to pass through and be released on the other side (sugars, amino acids, nucleosides)
Channel Proteins
Form open pores through. the membrane to allow free diffusion of any molecule of the appropriate size and charge
Glucose Transporters
Function by alternating between 2 conformational states, glucose-binding site is alternately exposed on the outside and inside of the cell
Glucose Concentration in the Cell
Rapidly metabolized in the cell so concentration remains low inside the cell and glucose is transported in, reversed in liver cells
Porins
Channel proteins that form open pores in the membrane that allow molecules to pass freely
Aquaporins
Allow water molecules to cross the membrane rapidly, impermeable to charged ions to allow passage of water without affecting electrochemical gradients
Ion Channels
Opening and closing is responsible for transmission of electrical signals, transport is extremely rapid, well studied in nerve and muscle cells, highly selective
Ligand-Gated Channels
Open in response to binding of neurotransmitters or other signalling molecules
Voltage-Gated Channles
Open in response to changes in electric potential across the plasma membrane
Ion Pumps
Use energy from ATP hydrolysis to actively transport ions across the plasma membrane to maintain concentration gradients
Na+ and the Cell
Pumped in
K+ and the Cell
Pumped out, plasma membrane has open K+ channels so flow of K+ makes the largest contribution to resting membrane potential
Nernst Equation
Describes the relationship between ion concentration and membrane potential
Action Potentials
Nerve impulses that travel along axons, membrane depolarizes as they travel (-60 to +30 mV in less than a millisecond)
Active Transport
Molecules are transported against their concentration gradients, energy is provided by a coupled reaction
Ion Pumps
Active transport of ions against their electrochemical gradients
ABC Transporters
Have highly conserved ATP-binding domains or ATP-binding cassettes, transport nutrients and waste into (prokaryotes) and out of cells (both)
MDR Transporters
Product of the multidrug resistance gene, remove toxic foreign compounds from cells, high levels in cancer cells and can remove a variety of chemo drugs
CF Gene
Encodes a protein in the ABC transporter family but a mutation interferes with the proper folding of the protein, defective Cl- transport in epithelial cells results in super thick and sticky mucus that obstructs respiratory pathways
Glucose Transporters in the Apical Domain of Intestine Epithelial Cells
Transport 2 Na+ and one glucose into the cell, flow of Na+ down its electrochemical gradient provides the energy for the uptake of glucose against its concentration gradient
Glucose Transporters in the Basolateral Domain of Intestine Epithelial Cells
Glucose is transferred to the underlying connective tissue and blood capillaries by facilitated diffusion, driven by Na+-K+ pumps
Symport
Transport of 2 molecules in the same direction
Uniport
Transport of a single molecule
Antiport
Transport of 2 molecules in opposite directions
Endocytosis
Allows cells to take up macromolecules, fluids, and large particles like bacteria. Material is surrounded by an area of plasma membrane that buds off inside the cell to form a vesicle containing the ingested material.
Phagocytosis
Cell eating, binding of a particle to receptors on cell surface triggers extension of pseudopodia that surround the particle and fuse to form a phagosome
Phagolysosomes
Phagosomes fuse with lysosomes and material is digested by acid hydrolases
Phagocytosis in Amoebas
Used to capture bacteria as food
Phagocytosis in Multicellular Animals
Used as a defence against invading microorganisms and to eliminate aged or damaged cells, WBCs in mammals
Macropinocytosis
Uptake of extracellular fluids in large vesicles
Lamellipodia
Sheet-like projections of the plasma membrane that curve into open cups, used in macropinocytosis
Clathrin-Mediated Endocytosis
Mechanism for selective uptake of specific macromolecules
Clathrin-Coated Pits
Specialized regions to which macromolecules bin to cell surface receptors, bud from the membrane with the help of dynamin to form clathrin-coated vesicles that fuse with early endosomes
LDL Particles
Low density lipoprotein, form of cholesterol transport through the bloodstream
Clathrin-Independent Endocytosis
Does not involve specific membrane receptors or coated vesicles
What do many cancers arise from?
Problems in signalling pathways that control normal cell proliferation
Direct Cell-Cell Signalling
Direct interaction of a cell with its neighbour
Endocrine Signalling
Signalling molecules or hormones are secreted by specialized endocrine cells and carried through the circulation to target cells at distant body sites
Paracrine Signalling
Molecules released by one cell act on neighbouring target cells (ex: neurotransmitters)
Autocrine Signalling
Cells respond to signalling molecules that they produce themselves, abnormal leads to cancer
T Lymphocytes
Respond to antigens by making a growth factor that drives their own proliferation, amplifying the immune response
Cancer Cell
Produces a growth factor that it also responds to, driving its own unregulated proliferation
Intracellular Receptors
Respond to small hydrophobic molecules that can diffuse across the plasma membrane
Steroid Hormones
Synthesized from cholesterol, directly regulate gene expression
Corticosteroids
From the adrenal gland, glucocorticoids and mineralocorticoids
Glucocorticoids
Stimulate production of glucose
Mineralocorticoids
Act on the kidneys to regulate salt and water balance
Ecdysone
An insect hormone that triggers metamorphosis of larvae to adults
Brassinosteroids
Plant steroid hormones that control several processes, including cell growth and differentiation
Thyroid Hormone
Synthesized from tyrosine in the thyroid gland, important in development and metabolism
Vitamin D3
Regulates Ca2+ metabolism and bone growth
Retinoic Acid and Retinoids
Synthesized from vitamin A, important in vertebrate development
Glucocorticoid Binding
Bound to Hsp 90 chaperones in the absence of hormone, glucocorticoid binding displaces Hsp90 and leads to binding of regulatory DNA sequences
Hormone Binding
In absence of hormone, thyroid hormone receptor is associated with a corepressor complex and represses transcription of target genes. Hormone binding results in activation of transcription.
NO
Nitric oxide, paracrine signalling molecule in nervous/immune/circulatory systems, can cross plasma membrane and alter activity of enzymes, synthesized from arginine, action is local bc extremely unstable
Guanylyl Cyclase
Main target of NO, binding of NO stimulates synthesis of a second messenger (cyclic GMP)
Second Messenger
Molecule that relays a signal from a receptor to a target inside the cell
NO in Circulatory System
Can signal dilation of blood vessels
NO in Muscles
Diffuses to smooth muscles and stimulates cGMP production
cGMP
Induces muscle cell relaxation and blood vessel dilation
CO as a Signalling Molecule
In nervous system, related to NO and acts similarly as a neurotransmitter and mediator of blood vessel dilation
Neurotransmitters
Carry signals between neutrons or between neutrons and other cells, released when an action potential arrives at the end of the neuron, neurotransmitters then diffuse across the synaptic cleft and bind to receptors on the target cell surface
Neurotransmitters and the Plasma Membrane
Hydrophilic so can’t cross and must bind to cell surface receptors, binding opens the channels
G Proteins
A major group of signalling molecules that link cell surface receptors to intracellular responses
Peptide Hormones
Include insulin, glucagon, and pituitary gland hormones
Neuropeptides
Secretes by some neurons
Neurohormones
Natural analgesics that decrease pain responses, bind to the same receptors on brain cells as morphine does
NGF
Nerve growth factor, regulates development and survival of neurons
EGF
Epidermal growth factor, stimulates cell proliferation, prototype for the study of growth factors
PDGF
Platlet-derived growth factor, stored in blood platelets and released during blood clotting at the site of a wound, stimulates proliferation of fibroblasts that contribute to regrowth of the damaged tissue
Cytokines
Regulate development and differentiation of blood cells and activities of lymphocytes during the immune response
Membrane-Anchored Growth Factors
Remain with the plasma membrane and function as signalling molecules in direct cell-cell interactions
Eicosanoids
Lipid signalling molecules that include prostaglandins, prostacyclin, thromboxanes, and leukotrienes. Break down rapidly and act in autocrine or paracrine pathways. Synthesized from arachidonic acid.
Arachidonic acid
Converted to prostaglandin H2, catalyzed by cyclooxygenase
Cyclooxygenase
Target of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs)
Prostaglandins
Inhibiting synthesis reduces inflammation and pain
Thromboxane
By inhibiting synthesis, aspirin reduces lately aggregation and blood clotting so small doses are prescribed for stroke prevention
Aspirin and NSAIDs
Been found to reduce frequency of colon cancer by inhibiting synthesis of prostaglandins that stimulate cell proliferation
Forms of Cyclooxygenase
COX-1 and COX-2
COX-1
Forms of cyclooxygenase that results in normal production of prostaglandins
COX-2
Forms of cyclooxygenase that results in increased prostaglandin production associated with inflammation and disease, selectively inhibited by some drugs
Gibberellins
Plant hormone for stem elongation
Auxins
Plant hormone for cell elongation by weakening the cell wall, also regulate aspects of plant development (cell division and differentiation), controls gene expression
Ethylene
Plant hormone for fruit ripening
Cytokinins
Plant hormone for cell division
Abscisic Acid
Plant hormone for onset of dormancy
How do auxins control gene expression?
By binding to and activating a receptor associated with a ubiquitin ligase
Intracellular Signal Transduction
Surface receptors regulate intracellular enzymes, which then transmit signals from the receptor to a series of additional intracellular targets
G Protein-Coupled Receptors
Signals are transmitted via guanine nucleotide-binding proteins (G proteins). Binding of ligand induces conformational change that allows cytosolic domain to activate G protein on inner face of plasma membrane. Activated G protein then dissociates from receptor and carries the signal to an intracellular target.
cAMP
Cyclic AMP - a second messenger that mediates responses in many hormones
Heterotrimeric G Proteins
3 subunits of G proteins (alpha, beta, gamma)
G Protein Alpha Subunit
Binds guanine, which regulates G protein activity, bound to GDP in the inactive state in a complex with beta and gamma. Hormone binding to the receptor exchanges GTP for GDP
Protein Kinase A in Glycogen Metabolism
Phosphorylase kinase is activated and in turn activates glycogen phosphorylase, which catalyzes glycogen breakdown. Glycogen synthase is inactivated so glycogen synthesis is blocked.
Signal Amplification
Binding of a hormone molecule leads to activation of many intracellular target enzymes
cAMP in Animal Cells
Increases in cAMP activate transcription of genes that have a regulatory sequence called cAMP response element
cAMP and Odour
A second messenger in sensing smells. Odorant receptors are G protein-coupled and stimulate adenylyl cyclase that leads to increased cAMP. cAMP opens Na+ channels in the plasma membrane, leading to initiation of a nerve impulse.
Cyclic GMP
Second messenger, mediates biological responses such as blood vessel dilation
cGMP in Vertebrate Eye
Converts visual signals to nerve impulses
Rhodopsin
Photoreceptor in retinal rod cells, G protein-coupled receptor, activated when light is absorbed by the associated molecule
Transducin
G protein activated by rhodopsin that stimulates cGMP phosphodiesterase
cGMP phosphodiesterase
Leads to decreased levels of cGMP
Tyrosine Kinases
Cell Surface receptors that phosphorylate their substrates on tyrosine residues
Receptor Tyrosine Kinases
Includes receptors for most polypeptide growth factors. All have N-terminal extracellular ligand-binding domain, transmembrane alpha helix, and cytosolic C-termincal domain with protein-tyrosine kinase activity
Binding of Ligands to Receptor Tyrosine Kinases
Binding to extracellular domains activates the cytosolic kinase domains, resulting in phosphorylation of both the receptors and intracellular target proteins that propagate the signal
Roles of Autophosphorylation
Phosphorylation of tyrosine in the catalytic domain increases protein kinase activity. Phosphorylation of tyrosine outside the catalytic domain creates binding sites for other proteins that transmit signals downstream from the activated receptors.
Downstream Signalling Molecules
Have domains that bind to specific phosphotyrosine-containing peptides of the activated receptors
SH2 Domains
Domain on downstream signalling molecules
Non-Receptor Tyrosine Kinases
Stimulate intracellular tyrosine kinases with which they are noncovalently associated
