Cell Adhesion Flashcards
What is an Ig-CAM? is it calcium dep or not? hetero or homophilic? what types of diseases from mutations? which virus? list characteristics.
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
Proteoglycans list characteristics and give examples
transmembrane ca-independent bind epithelial cell to collagen matrix ECM glycan side chains to bind growth factors ex: CD44 stem cell
Selectins. how are they super specific and what types of cells use them/how are they used??
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.
integrins..structure? what do they bind?? where are they most found?
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
What is the cadherin structure like? what does binding to a certain ion do to it?
5 domains of conserved repeats that bind calcium in ectodomain. beta barrell. calcium rigidifies it
name the CA dependent and CA independent CAMs
ca independent= proteoglycans; Igg ca dependent= integrins, cadherinsm selectins
where are the cis and trans dimers in cadherin?
cis on same cell and trans bw neighboring cells
are cadherins homo or hetero philic?
mainly homophilic but can be hetero
E and N cadherin refer to???
epithelial and neural, segregate w their kind
What are the 2 functions of cadherins? As for the 2nd function…what are the two types?
- initiating adhesion 2. forming adhesion clusters…(desmosomes and adherens junctions)
Name the 5 components of adherens structure and describte the function of each
P120 prevents cadherin endocytosis
Plakoglobin/b-catenin form modulatable links bw cadherins and a-cat
A-cat regulates actin assembly
What are the three different shapes/structures that adherens junctions can take?
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.
What types of cancer can loss of E-cadherin result in? what else is often loss thats is part of the adherens junction?
breast and gastric.
a-catenin
b-catenin is both
- a bridge between……and…
- usually degraded by**** pathway which can result in colon cancer when misregulated or overexpressed. its usually degraded to prevent tumor formation
alpha catenin and cadherins
WNT signalling…APC usually degrades it too
What are the function of desmosomes?
the dont initiate but rather reinforce cell to cell adhesion
Where are desmosomes (aka which tissues specifically)
all epithelial but especially stressed tissues like skin and heart
What are the specific structural features of desmosomes? what distinguishes them visually from adherens?
suspenders w buttons, tensile web
electron dense plaques beneath plasma are more pronounced
bistected by midline
wider extracellular gap than adherens
desribe how desmosomes attach to IF (molecular architecture)
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
Which cytoskeletal linker proteins bind to intermediate filaments in desmosomes and hemidesmosomes respectively?
hemi-BPAG1
desmo-desmoplakin
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?
Desmoplakin and plakoglobin
fragile skin and broken hearts!
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?
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
plakoglobin autosomal recessive deletion in C terminus causes what disease w what symptoms by what mech?
whats the desmoplakin disease?
Naxos wooly hair, crack palms, cardiomyopathy
bridge broken to cytoskeleton
Carvajal is desmoplakin
What is AC?
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
