EXAM 3 STARTS: Cell adhesion Flashcards
how do cells define their capacity for adhesive interactions
by selectively expressing plasma membrane receptors with limited ligan-binding activity
how are receptors expressed
mostly genetically but sometimes by extracellular stimuli
what is the second principle of adhesion
many adhesion proteins bind one main ligand and many ligands bind a single type of receptor
what makes the integrin family of receptors an exception to one-to-one pairing
they bind more than one ligand and some ligands, such as fibronectin, bind more than one integrin. they also bind ahdesion proteins on the surface of other cells including Ig-CAMs and one cadherin
describe how cadherins prefer to bind and what does binding require
prefer to bind themselves so they promote the adhesion of like cells. it requires Ca2+
describe how selectins bind
anionic polysaccharides like those on mucins. generally these interactions bind together two different types of cells
describe how Ig-CAMs bind
they bind other cell surface adhesion proteins. may occur between the same or different cell types
how do cells modulate adhesion
by controlling the surface density, state of aggregation, and state of activation of their adhesion receptors
what does surface density reflect
level of synthesis, partitioning of adhesion molecules between the plasma membrane and intracellular storage compartments
how can cells sort themselves
according to the type and level of cadherins they express
what are cadherins
calcium dependent adhesion molecules
what do cadherins do
establish and maintain intercellular connections
- spatial segregation of cell types
what anchors cadherins into the cell
a complex of proteins called catenins
what forms the adherens junctions
cadherin-catenin complex
where do catenins bind
the actin cytoskeleton of the cell
how well do cell surface adhesion proteins bind their ligands
weakly in comparison to other molecular interactions
what do rapid, reversible binding of ligands (transient adhesion) allow for
-white blood cells to roll along the endothelium of blood vessels
- fibroblasts to migrate through CT
where do many adhesion receptors interact
within the cytoskeleton inside the cell
what do adapter proteins link
cadherins and integrins to actin filaments or intermediate filaments
what is the purpose of adapter protein linkage of cadherins and integrins to actin filaments or intermediate filaments
provide mechanical continuity from cell to cell in muscles and epithelia, allowing them to transmit forces and resist mechanical disruption
what does the association of ligands and adhesion receptors activate
intracellular signal transduction pathways, leading to changes in gene expression, cellular differentiation, secretion, motility, receptor activation and cell division
how do cells attach to the underlying extracellular matrix
-focal adhesions- attach the actin cytoskeleton to fibers of fibronectin
- hemidesmosomes- connect intermediate filaments to basal laminae
where are integrin-containing cell matrix junctions found
highly motile cells such as keratinocytes and in immobile strongly adherent cells such as epithelila
- weakly adherent
where are hemidesmosomes found
mainly on the basal surface of epithelial cells
what do hemidesmosomes do
firmly anchor epithelial cells to underlying basal lamina
what does the cytosolic side of a hemidesmosome consist of
a plaque composed of adapter proteins which are attached to the ends of keratin filaments
what is integrin alpha6beta4 localized to and what does it bind to
localized to hemidesmosomes and binds to plectin within the plaques and to laminin
how do cell-matrix junctions increase the overall rigidity of epithelial tissues
by interconnecting the intermediate filaments of the cytoskeleton with the fibers of the basal lamina
where is E-cadherin expressed
on all early mammilian embryonic cells, even at the 1-cell stage. later- restricted to epithelial tissues of embryos and adults
where is P-cadherin expressed
trophoblast cells ( placental cells of the mammilian embryo that contact the uterine wall) and on the uterine wall epithelium
what does P cadherin do
facilitates the connection of the embryo to the uterus
what do protocadherins do
separate the notochord from the other mesodermal tissues during xenopus gastrulation
where is N-cadherin expressed
first on mesodermal cells in the gastrulating embryo as they lose their E-cadherin expression. also highly expressed on cells of the developing CNS
what does EP-cadherin do
critical for maintaining adhesion between the blastomeres of the xenopus blastula and is required for the normal movements of gastrulation
what are protocadherins
calcium dependent adhesion proteins that differ from the classic cadhering in that they lack connections to the cytoskeleton through catenins
what is homophilic binding
-cadherin joins cells together by binding same type of cadherin
example: E-cadherins will stick best to other cells with E-cadherin and will sort out from cells containing N-cadherin
how can cadherins be restricted in their expression
spatially
what are the functions of the basal lamina
- molecular filter
-cell barrier - molecular scaffolding to aid in regeneration after injury
how does the basal lamina act as a molecular filter
retaining proteins in the blood while filtering toxic substances into the urine
how does the basal lamina act as a cell barrier (example)
ameloblasts and odontoblasts separated by a BM during tooth development
what does vinculin do when interacting with Arp2/3
at focal adhesions the leading edge promotes protrusion of the membrane
what does vinculin do in traction force generation
links integrins to the actin cytoskeleton and bears the forces exerted during motility
how does vinculin interact with PIP2
induces a conformational change that reduces vinculin interaction with actin, therby promoting the disassembly of focal adhesions
how do t-cells use cell adhesion receptors
in process of antigen presentation
how does mechanical tension activate signaling pathways at adhesion sites
exposure of cryptic sites, tension can affect protein conformation to expose protein binding sites or sites for kinases or other protein modifications
how does RhoA regulate adhesion maturation through Rock and mDia
-adhesion of fibronecting activates RhoA through p115/RhoGEF and LARG, leading to rock mediated myosin stimulation.
-GEF-H1, LARG, and mDia are recruited and promote actin polymerization
-B1 and alphav integrin subtypes cooperate to regulate RhoA signaling and adhesion maturation
how do cells transition to a motile state
de-adhesion of cells from the ECM by inhibition of cell-matrix interactions and by destruction of matrix components
what do the main class of disintegrins contain
integrin-binding RGD sequence in ECM proteins
what do disintegrins do
bind to integrins on the surface of cells and competitively inhibit binding of cells to matrix components
what does the secondary class of disintegrins contain
2 proteases: ADAMs and MMPs
what are ADAMs and what do they do
membrane bound proteases that catalyze shedding of transmembrane proteins
-soluble enzyme that cleaves non-fibrillary ECM proteins
what do tight junctions do
seal gap between epithelial cells
what do adherens junctions do
connect actin filaments between cells
what do desmosomes do
connects intermediate filaments between cells
what do gap junctions do
allow passage of small water soluble molecules from cell to cell
what do hemidesmosomes do
anchor intermediate filaments in cell to ECM
what are the cell- cell junction types and what is their transmembrane adhesion protein
adherens and desmosome and cadherin
what are the cell-matrix junction types and what is their transmembrane adhesion protein
actin-linked cell-matric adhesion and hemidesmosomes and they use integrins
