Cell Junctions and Adhesion Flashcards
what type of cell junction is NOT associated with cytoskeletal components?
and what is the function of this cell junction
gap (communicating) junctions: connect adjacent cells, formed by many clustered connexons, pass small molecules between cells
which types of cell junctions are associated with actin filaments and what are their functions?
tight (occluding) junctions: belt around cell, control passage of substances between adjacent cells, define cell polarity, found at apical side
zonula adherens/ belt desmosomes: anchorage between cells
which types of cell junctions are associated with intermediate filaments and what are their functions?
macula adherens/ spot desmosomes: spot-like anchorage between cells
hemidesmosomes: link basal domain of epithelial cells to basal lamina (cell-matrix adhesion)
what kind of trans-membrane proteins do belt and spot desmosomes use? what about hemi-desmosomes?
belt and spot (cell-cell): cadherins (CAlcium Dependent ADHERIN proteins)
hemi (cell-matrix): integrin (alpha6beta4)
what kind of trans-membrane proteins do occluding (tight) junctions use?
occludins: associate with occludins of other cells
claudins: regulate paracellular permeability
actin cytoskeleton associated
how do claudin proteins function in renal tubules?
claudins are transmembrane proteins in tight (occluding) junctions
claudins 16 and 19 expressed highly where calcium and magnesium reabsorption take place - assist with reabsorption
regulate paracellular permeability
if a patient had a genetic mutation in Claudin 19, what might you expect their serum Mg2+ and urinary calcium to be relative to the norm?
claudins are tight junction proteins, regulate paracellular permeability and reabsorption of magnesium and calcium in renal tubules
would see LOW serum Mg2+ and HIGH urinary Ca2+
(lack of reabsorption)
what type of cell junction controls apical constriction and invagination? (give both names)
belt desmosomes = zonula adherens or adherens junctions
apical actomyosin complex contracts to buckle epithelium (apical portions narrower than basal portions)
for this reason belt desmosomes are closer to the apical side of cell, right after tight junctions
what are cadherins
CAlcium-dependent ADHerens proteINs
single transmembrane proteins with large extracellular domain for calcium binding - Ca2+ dependent
form cis-homophilic dimer (interact with same kind of cadherins)
cadherins are main adhesion protein holding epithelial cells together in sheet arrangement
in epithelial cells, E-cadherin mediated adhesion is essential in _____ before _____ can form
E-cadherins in belt desmosomes need to come together before tight junctions can form (via occludins and claudins)
cadherins are main adhesion protein for holding epithelial cells in sheets
what happens when E-cadherins function is lost?
EMT: epitelial mesenchymal transition (EMT) during cancer progression
main adhesion protein for holding epithelial cells in sheets - without it, cells become mesenchymal, lose polarity and cell adhesion, gain ability to migrate
you learn that P-cadherin is expressed in retinal pigment epithelia and hair follicles. Would would you expect then in a p-cadherin mutation?
balding and vision loss
loss of cell-cell adhesion
you’re looking at a tissue biopsy from a cancer patient. you see epithelial cells that have lost polarity and cell-cell adhesion, and have begun to migrate and invade neighboring tissue. what is this process called and what went wrong?
loss of E-cadherin —> epithelial mesenychmal transition (EMT)
what type of cell junction provides strongest source of mechanical strength between cells?
spot desmosomes/macula adherens
made of intermediate filaments (“tendons” of the cell)
what are the characteristics of integrin proteins and what cell junctions are they associated with?
mediate interactions between inside the cell and ECM
found in hemidesmosomes and focal adhesions (cell-matrix of basal lamina)
2 subunits, alpha and beta subunits
contrast pemphigus and pemphigoid blistering diseases
pemphigus: autoantibodies against spot desmosomes (between cells), blisters within epidermis
pemphigoid: autoantibodies against hemidesmosomes (between cell and basal lamina - dermis), blisters between epidermis and dermis
you have 2 patients with blistering disease. however, they differ in the location of their blisters. Patient 1 has blisters within their epidermis, while Patient 2 has blisters between their epidermis and dermis.
What are each of these forms of blistering disease called, and what is going wrong?
Patient 1: autoantibodies against spot desmosomes —> pemphigus
Patient 2: autoantibodies against hemidesmosomes —> pemphigoid
describe how levels of calcium can affect connexon channel permeability in gap junctions
low calcium - open
high calcium is a signal of apoptosis of neighboring cells - channels close to protect cell
gap junction gating regulated by pH, voltage, metabolites
where are connexin 26 and 32 found and what is the clinical implication of a mutation in each?
connexin 26: found in cochlear hair cells, mutation = deafness
connexin 32: found in peripheral myelin, mutation = peripheral neuropathy
connexin are important protein of gap junctions
what is the general structure and function of selectin proteins
single transmembrane cell adhesion molecules (non-junctional)
calcium dependent, carbohydrate recognition domain in extracellular domain
what is the function of CAMs and what protein superfamily do they belong to?
cell adhesions molecules - important for non-junctional cell adherence
ICAM = intercellular CAM
VCAM = vascular CAM
NCAM = neural CAM
belong to immunoglobulin (IG) superfamily because the extracellular domain is folded into 2-6 Ig-like domains
what non-junctional cell adhesion molecules are important for leukocyte extravasation?
- selectin phase: selectins on endothelial cell surface binds carbohydrate ligands on leukocyte surface
- integrin phase: integrin receptors for endothelial CAM are activated on leukocyte surface during leukocyte (neutrophil) rolling. Activated integrins strengthen leukocyte binding to endothelial cell surface
what causes pemphigus
autoantibodies against spot desmosomes (anchored to intermediate filaments)
causes blisters within epidermis
