Cell Junctions and Adhesion

Question 1

what type of cell junction is NOT associated with cytoskeletal components?

and what is the function of this cell junction

Answer 1

gap (communicating) junctions: connect adjacent cells, formed by many clustered connexons, pass small molecules between cells

Question 2

which types of cell junctions are associated with actin filaments and what are their functions?

Answer 2

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

Question 3

which types of cell junctions are associated with intermediate filaments and what are their functions?

Answer 3

macula adherens/ spot desmosomes: spot-like anchorage between cells

hemidesmosomes: link basal domain of epithelial cells to basal lamina (cell-matrix adhesion)

Question 4

what kind of trans-membrane proteins do belt and spot desmosomes use? what about hemi-desmosomes?

Answer 4

belt and spot (cell-cell): cadherins (CAlcium Dependent ADHERIN proteins)

hemi (cell-matrix): integrin (alpha6beta4)

Question 5

what kind of trans-membrane proteins do occluding (tight) junctions use?

Answer 5

occludins: associate with occludins of other cells

claudins: regulate paracellular permeability

actin cytoskeleton associated

Question 6

how do claudin proteins function in renal tubules?

Answer 6

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

Question 7

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?

Answer 7

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)

Question 8

what type of cell junction controls apical constriction and invagination? (give both names)

Answer 8

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

Question 9

what are cadherins

Answer 9

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

Question 10

in epithelial cells, E-cadherin mediated adhesion is essential in _____ before _____ can form

Answer 10

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

Question 11

what happens when E-cadherins function is lost?

Answer 11

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

Question 12

you learn that P-cadherin is expressed in retinal pigment epithelia and hair follicles. Would would you expect then in a p-cadherin mutation?

Answer 12

balding and vision loss

loss of cell-cell adhesion

Question 13

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?

Answer 13

loss of E-cadherin —> epithelial mesenychmal transition (EMT)

Question 14

what type of cell junction provides strongest source of mechanical strength between cells?

Answer 14

spot desmosomes/macula adherens

made of intermediate filaments (“tendons” of the cell)

Question 15

what are the characteristics of integrin proteins and what cell junctions are they associated with?

Answer 15

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

Question 16

contrast pemphigus and pemphigoid blistering diseases

Answer 16

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

Question 17

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?

Answer 17

Patient 1: autoantibodies against spot desmosomes —> pemphigus

Patient 2: autoantibodies against hemidesmosomes —> pemphigoid

Question 18

describe how levels of calcium can affect connexon channel permeability in gap junctions

Answer 18

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

Question 19

where are connexin 26 and 32 found and what is the clinical implication of a mutation in each?

Answer 19

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

Question 20

what is the general structure and function of selectin proteins

Answer 20

single transmembrane cell adhesion molecules (non-junctional)

calcium dependent, carbohydrate recognition domain in extracellular domain

Question 21

what is the function of CAMs and what protein superfamily do they belong to?

Answer 21

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

Question 22

what non-junctional cell adhesion molecules are important for leukocyte extravasation?

Answer 22

1. selectin phase: selectins on endothelial cell surface binds carbohydrate ligands on leukocyte surface
2. 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

Question 23

what causes pemphigus

Answer 23

autoantibodies against spot desmosomes (anchored to intermediate filaments)

causes blisters within epidermis