Lecture 24 - Interactions Between Cells and Their Environment Flashcards
def: a collection of structurally similar cells that cooperate tp perform a specific function
tissue
where did all the proteins outside a cell originally come from?
inside the cell
what are the 3 roles of the ECM?
- helps determine cell shape
- provides physical support for cells
- plays a regulatory role in cell signalling
what are the 3 types of extracellular matrix?
- bone
- cartilage
- connective tissue
def: hard calcified ECM that contains a small number of interspersed cells
bone
def: cells are imbedded in a flexible ECM rich in proteoglycans
cartilage
def: gelatinous ECM surrounding glands and blood vessels
connective tissue
def: structural proteins that provide strength and flexibility
collagens/elastins
def: components of hydrated matrix
proteoglycans
def: adhesive/connective glycoproteins that allow cells to attach to the ECM
fibronectin/laminins
what is the most abundant protein in the human body ?
family of closely related collagens, which form fibres with high tensile strength
collagen is secreted by several types of cells in connective tissues including __________-
fibroblasts
def: mutations in collagen resulting in the excessive looseness of skin and joints
ehlers-danos
def: a temporary collagen disease, because vitamin C is a co-factor in collagen synthesis
scurvy
all collagens occur as a ________, with rigid triple helix of intertwined polypeptides, _______ chains
trimer, alpha
collagens are very rich in:
glycine, proline and lysine
no vitamin C results in what in terms of collagen?
no hydroxyls can be added which means weaker interactions
def: three alpha chains assemble to form a triple helix, with short non-helical sequences at both ends
procollagen
once procollagen is secreted out of the cell, what cleaves it and removes it from both ends of the molecule?
procollagen peptidase
collagen has tensile strength but not enough for some types of tissue, in these cases elasticity is provided by ________
elastins
def: rich in glycine and proline, molecules are cross-linked by covalent bonds between lysine residues
elastins
with time, what happens to elastins?
they’re lost from tissues and skin will wrinkle and joints are less flexible
def: meshed gel-like network of collagen and elastin fibers
proteoglycans
def: large carbohydrates with repeating disaccharide units
glycosaminoglycans (GAGs)
what are the most common types of GAGs?
- chondroitin sulfate
- keratan sulfate
- hyaluronate
the presence of charged sulphate and carboxyl groups attract ______, which bind water, creating a hydrated and gelatinous matrix
cations
most GAGs in the ECM are ___________ _________ ____________ to form proteoglycans
covalently bound to proteins
def: reinforce direct links between the ECM and the plasma membrane
adhesive glycoproteins
what are the most common adhesive glycoproteins?
fibronectins and laminins
what is the structural composition of fibronectin?
consists of 2 very large polypeptide subunits linked near the C-terminus by disulfide bonds
what do the functional units of fibronectin bind?
- numerous components of the ECM
- bind receptors on the cell surface
def: family of proteins with three subunits linked together by disulfide bonds
laminins
what can bind to the binding sites on laminins?
- collagen
- proteoglycans
- other laminins
- receptors on cell surfaces
where are laminins mainly found?
in the basal lamina as a thin sheet of specialized extra cellular material
integrins integrate the _____ and ______ cellular environments
extra- and -intra
what do integrins do outside the cell?
bind to a diverse array of molecules
what do integrins do inside the cell?
interact with dozens of different proteins to influence cellular events
what is the physically composition of integrins?
two large transmembrane polypeptides, an alpha and beta chain, which are non-covalently linked to each other
how do integrins differ each other?
binding specificity, subunit size and tissue distribution
where is the ECM binding site of an integrin?
the extracellular domains of the alpha and beta chains, right in the cleft between the chains
what are the 2 confirmations of integrins and what do they correspond to?
- bent - inactive and cannot bind
- upright = active and ligand bound
what does the intracellular domain of an integral do?
binds proteins like Talin, which separates the alpha and beta chains and activates the integrins
what are the 2 types of activity integrins are impacted in ?
adehesion and signal transduction
def: intracellular signalling can induce integrity clustering, which effect ECM binding
“inside out” signalling
def: integrins can act as receptors that activate intracellular signalling cascades
“outside-in” signalling
for most cells to grow in culture, they must be attached to ___________, if they can’t attach to an ECM layer, they will stop dividing
substratum
def: the need to cells to be attached to a substratum in order to grow and divide, involves the activation of intracellular pathways following integral clustering at focal adhesion
anchorage dependent growth
in vitro, anchorage dependent growth requires attachment of a cell to the substratum, this occurs in stages at discrete sites called _________ __________
focal adhesions
how to integrins interact with actin microfilaments?
via linker proteins talin, vinculin, and alpha actinin
def: the tightest attachment between a cell and its ECM occur at these special adhesive structures
hemidesmosomes
where are hemidesomosomes found?
in epithelial cells, they contain integrins and attachch a cell to a substrate, like the basal lamina
in hemidesmosomes, integrins are attached to the ________________ protein _______________
intermediate filament protein keratin
the linker proteins in hemidesmosomes form _ ________ ________, connecting the integrins to the cytoskeleton
a dense plaque
what are the 4 families of cell adhesion molecules? (CAMs)
- integrins
- catherins
- selectins
- Ig-superfamily
which CAM has Ca2+ dependent binding?
cadherins
which CAM has Ca2+ independent binding?
Ig-superfamily
def: may be the most important proteins in molding cells into cohesive tissue and holding the tissue together
cadherins
what are the physical properties of a cadherin?
- small cytoplasmic domain
- single membrane spanning domain
- large extracellular component, consisting of 5 domains of similar size and strucutre
what provides rigidity to the cadherin strucures, allowing them to zip together?
Ca2+ binding between the domains
beta catenin and alpha catnenin bind to the ________ ________ of cadherin and that recruits actin to the membrane
cytosolic tail
what are the 2 roles of catenin proteins?
- tethering the cadherin to the cytoskeleton
- transmitting extracellular signals to the cytoplasm and nucleus
def: compound that binds to a specific carbohydrate group
selectin
what is the physical composition of a selectin?
- small cytoplasmic domain
- single membrane spanning domain
- large extracellular component, consisting of a number of domains ending in the lectin-binding domain
when a wall of a blood vessel receives a chemical signal that there is nearby damage, what happens?
activated endothelial cells display P-and E-selectins to “capture” a neutrophil that is rolling along the wall
what part of the endothelial cell surface bind to the receptor on a neutrophil and triggers a signal cascade that activates integrins
the phospholipid platelet activating factor (PAF)
what stops the rolling of a neutrophil?
the ICAM and integrins interacition
what are the 3 common types of junctions within animal cells?
- adhesive junctions (adherens junctions and desmosomes)
- tight junctions
- gap junctions
which cell junctions create adhesion points?
adherens junctions and desmosomes
which cell junctions seal the space between cells?
tight junctions
which cell junctions form communication ports between cells?
gap junctions
what are adherens junctions made of?
CAMs and cadherins
what are desmosomes made of?
CAMs and cadherins
what are tight junctions made of?
occluding and claudins
what are gap junctions made of?
connexins
def: form a continuous belt that encircles the cell near the apical end of the lateral membranes, prominent in epithelial cells of the kidney
adherens junctions
how big is the space left by adherens junctions?
30 nm
adherens junctions are ___________ ____________ junctions that interact with _________________
cadherin-mediated, microfilaments
def: disk-shaped points of strong adhesion between adjacent cells in a tissue, abundant in cells that experience mechanical stress
desmosomes
def: extracellular space of 30 nm between the two connected cells
desmosome core
desmosomes rely on _________ _________ _______ which indirectly interact with ____________ _________
desmosomal-specific catherine, intermediate filaments
the beta-catenin family protein ___________ binds the cadherins, and the linker protein ________________
plakoglobin, desmoplakin
what does desmoplakin bind to?
intermediate proteins, such as vimentin, design, and keratin
what do tight junctions enforce?
force transport through the cell rather than around
where do tight junctions form?
at the apical end of the lateral surfaces of each cell
scaffolding proteins at tight junctions recruit proteins such as _________ to the junctions
F-actin
how do tight junctions block lateral movement of lipids and proteins in the plasma membrane?
- lipids is blocked only in the outer monolayer/leaflet
- integral membrane proteins are completely blocked since they cross both leaflets
what do the large extracellular loops of claudin do in tight junctions ?
form ion-selective pores to allow passage of specific ions
def: region where the plasma membrane of cells are aligned and brought into contact, with a very small gap between (3nm)
gap junction
at a gap junction, the plasma membranes of adjacent cells are joined by 2 hollow cylinders, called ___________, which are highly linked to each other by noncovalent interactions
connexons
__________ are assemblies of 6 integral membrane subunits of _____________ proteins which form a circle
connexon, connexin
T or F: connexon channels are non-selective
true
gap junctions are the site of what kind of communication?
GJIC (gap junction intracellular communication)
what kind of signals can be related by gap junctions?
- passed directly between cells, integrating cells into functional unist
- regulated by gating the channels
how are connexins selective within eachtoher?
they must be compatible to form a gap junction that works, if they are incompatible, they form incompatible connexons
