Cell Adhesion

Question 1

What is an Ig-CAM? is it calcium dep or not? hetero or homophilic? what types of diseases from mutations? which virus? list characteristics.

Answer 1

immunoglobulin like structure - ca-independent adhesion -involved in transient adhesion w neural homophilic ncam and heterophilic lymphocyte Lcam -cause inflammation asthma myelination issues rhino virus I-Cam

Question 2

Proteoglycans list characteristics and give examples

Answer 2

transmembrane ca-independent bind epithelial cell to collagen matrix ECM glycan side chains to bind growth factors ex: CD44 stem cell

Question 3

Selectins. how are they super specific and what types of cells use them/how are they used??

Answer 3

ca-dependent sugar binder! -N-terminal lectin binding domain recognizes sugars (more specifitity than proteins bc more structurally complex) to facilitate adhesion Selectin “lymphocyte homing receptors” recognize specific sugars on endothelial proteins termed “vascular addressins” and direct lymphocytic subpopulations to specific lymph nodes and sites of vascular inflammation.

Question 4

integrins..structure? what do they bind?? where are they most found?

Answer 4

ca dependent transmembrane 18 a 8 b transmembrane subunits -bind divalent cations (ca) which induce conf. change to allow adhesion -most bind ECM proteins of basal lamina to cytoskeleton -most found in desmosomes and focal contacts

Question 5

What is the cadherin structure like? what does binding to a certain ion do to it?

Answer 5

5 domains of conserved repeats that bind calcium in ectodomain. beta barrell. calcium rigidifies it

Question 6

name the CA dependent and CA independent CAMs

Answer 6

ca independent= proteoglycans; Igg ca dependent= integrins, cadherinsm selectins

Question 7

where are the cis and trans dimers in cadherin?

Answer 7

cis on same cell and trans bw neighboring cells

Question 8

are cadherins homo or hetero philic?

Answer 8

mainly homophilic but can be hetero

Question 9

E and N cadherin refer to???

Answer 9

epithelial and neural, segregate w their kind

Question 10

What are the 2 functions of cadherins? As for the 2nd function…what are the two types?

Answer 10

1. initiating adhesion 2. forming adhesion clusters…(desmosomes and adherens junctions)

Question 11

Name the 5 components of adherens structure and describte the function of each

Answer 11

P120 prevents cadherin endocytosis
Plakoglobin/b-catenin form modulatable links bw cadherins and a-cat
A-cat regulates actin assembly

Question 12

What are the three different shapes/structures that adherens junctions can take?

Answer 12

small points (punta adherens) of filopodial contact. patches (fascia adherens) within cardiac intercalated discs

a belt like area (zonula adherens) at the apex of polarized epithelial cells.

Question 13

What types of cancer can loss of E-cadherin result in? what else is often loss thats is part of the adherens junction?

Answer 13

breast and gastric.

a-catenin

Question 14

b-catenin is both

1. a bridge between……and…
2. usually degraded by**** pathway which can result in colon cancer when misregulated or overexpressed. its usually degraded to prevent tumor formation

Answer 14

alpha catenin and cadherins

WNT signalling…APC usually degrades it too

Question 15

What are the function of desmosomes?

Answer 15

the dont initiate but rather reinforce cell to cell adhesion

Question 16

Where are desmosomes (aka which tissues specifically)

Answer 16

all epithelial but especially stressed tissues like skin and heart

Question 17

What are the specific structural features of desmosomes? what distinguishes them visually from adherens?

Answer 17

suspenders w buttons, tensile web

electron dense plaques beneath plasma are more pronounced

bistected by midline

wider extracellular gap than adherens

Question 18

desribe how desmosomes attach to IF (molecular architecture)

Answer 18

desmosomal cadherins (dsg and dsc) bind directly to desmosomal catenins (PG and PP) to intermediate filament cytoskeletal linker protein (desmoplakin DP and plakophlin PP)that connect intermediate filaments (IF, keratin) to the plasma membrane.

Dsg = desmogleins

Dsc = dsmocollins

Pg = plakoglobin

DP = desmoplakins

PP = plakophilin

http://www.nature.com/nrg/journal/v3/n3/images/nrg758-f3.jpg

Question 19

Which cytoskeletal linker proteins bind to intermediate filaments in desmosomes and hemidesmosomes respectively?

Answer 19

hemi-BPAG1

desmo-desmoplakin

Question 20

which two proteins are highly conserved in desmosomal binding architecture that can have widespread deleterious effects if mutated?

in which tissues does a knockout in one of these present most?

Answer 20

Desmoplakin and plakoglobin

fragile skin and broken hearts!

Question 21

what are the three different forms of dsg (desmoglein) ? what diseases associated w each?

also what is the mech of class of diseases that attack these?

Answer 21

differ in cytoplasmic sequences

Dsg2 in basal cells

Dsg3 in the lower surabasal layers =Pemphigus vulgaris sera

Dsg1 in all suprabasal cells=Pemphigus foliaceus, staphlococcal scalded skin syndrome and bullous impetigo (bacterial!!)

antibodies attack dsg’s and disrupt keratinocytes=autoimmune blistering skin disease called pemphigus

Question 22

plakoglobin autosomal recessive deletion in C terminus causes what disease w what symptoms by what mech?

whats the desmoplakin disease?

Answer 22

Naxos wooly hair, crack palms, cardiomyopathy

bridge broken to cytoskeleton

Carvajal is desmoplakin

Question 23

What is AC?

Answer 23

Arhythmogenic Cardiomyopathy genetic. casued by desmosomal protein mutations. stable gap junctions cant form unless mechanical stress bearing there via adherens and desmosomes. structure and signalling messed up