S4 Flashcards
cell expression basic concept for N and E cadherin
can sort by type or by level of cellular expression
cell adheisoon molecuels vs cell junctions
membrane proteins vs aggregates of transmembrane and intracellular proteins
inuitive complexity, size, transience and stability differences
epithelial tissue
mechanical stress cell to cell by cytoskeletal filaments
anchored to cell matric and cell to cell adhestin sites
connective tissue
ECM directly bears mechanical stress
metastasis
cells leave tumor then enter blood stream then extravasation to new tissue to colonize
neural development and adhesion
cells in epitheliem and then lose adheision when dividing then adhere to radial glia to move up
anchoring junctions
actin filament attacchment sites
intermediate filament attatchment sites
actin filament attatchment sites
cell cell junctions (adherins junctions)
cell matrix junctions (actin linked cell matrix adhesions)
intermediate filament attatchment sites
cell cell is desmosomes
cell matrix is hemidesmosomes
Occluding junctions
tight junctions in vertes
septate in invertes
signal relay junctions
chemical synapses
immunological synnapes
transmembrane lignad - receptor and cell cell signaling contancts
role of extra junctional adehesion molecuels
involved in forming junctions but not direcly part of it
ways to measure adhesion/junction force
centrifugation atomic force microsopy dual pippette assay flipping assay magnetic bead FRET
this section TEM vs Freeze fracture TEM
close vs overview?
freeze fracture
separate leaflits of PM
E face is smooth exoplasmic
P face is rough protoplasmic
occluding junctions on endothelim of intestings
tight junctions
apical
usually top down is tight,adherin, desomosomal, hemidesmosomal
visible as terminal bar
protein occludin
sealing strands with actin microfilaments
polarize cells
2 anchoring junction protein types
intracellular anchoring proteins
transmembrane adheision proteins (adheision molecuels)
adherins junction
cell to cell classical cadheirins bind to same on other cell actin filaments alpha and beta cateinn
desomosomes
non classiscal cadherines cell to cell bind desmoglein and desmocollin on other cell intermediate filaments plakoglobin
adherens and development
contract to create invaginations for like epithelial tube
E cadherins outside tube
N cadherins in the ring
mechanotransduction
when stretched more actin recruited
hemi vs desmosome
both link to intermediate
hemi to basal lamina,
desmo is cell cell
pemphigus vulgaris
autoimmune disease affecting desomosmes
antibodies disrupt in skin causing blisters, flfluid loss and infection
hemidesmosomes in EM
look like half desmosomes
anchor basal lamina to intermediate filaments
disrupted in bullous pemphigold
focal adhesions
link actin to ECM
cell movement and wound healing
integreins
integrin activation
ligand for outside in or tallin for inside out
Talin as a mechanotradducoer
vinculin binding site exposed from tension
intracellular
selectins
adhesion molecules that dont participate in junctions
transient adhesions
extravasation
weak adhesion and rolling (selectin dependent)
strong adhesion and emigration (integrin dependent)
white blood cells leave blood stream to chase inflammation
neurexin and neurolign
involved in cell cell connections at synapes and signaling for developing and maintaintng neural contacts
integrin receptor basics
membrane spanning
bind to ECM proteins
transduce bidirectionsally
GAGs
glycosamino glyicans
amino sugar
4 groups mainly hylauran
hylauronan
simples GAG
not bownd to core protein
proteoglycan
GAGs covalentlybound to core preotiens
gel like ground substances
functions of GAGS and proteoglycans
regulate chemical signaling
regulate other secreted proteins
act as co receptors
resist compressive force
hurlers syndrome
accumulation of the GAG heparan sulfate
deficincy in degration enzyme
fibrous proteins in ECM
collagen
elastic fibers
fibronectin
collagen
tensile strength
triple helix
hydoxyproline and hydroxylisine residues are critical for fibril formation
cells determine size/ organizaation via gene expression
types of collagen
I most comman for like skin and bone
IX and XII for link fibrils
IV network forming
VII anchorning
collagen assembly steps
syn of pro alpha chain hydroxylation of prolines and lysines glycosylation of selected hydroxylysines self assmbly of 3 pro alhpha chains procollagen triple helix formation via inter chain H bonds at hydroxylated residues secretion cleaveage of propetides self aseembly into crosslinked fibriles
fibril associated collagens
wickerwork is perpindicular
budneled is parallel
scurvy
vitamin C deficiency
no hydroxylation so no collagen
osteogeneis imperfecta
colllagen Type I mutated
weak bones
scleroderma
autoimmune scar tissue buildup and collagen in dkinand organs
elastic fibers
recoil after trasent stretch
elastin with loos random coil model
microfibril coat eleastin core as scaffold made of fibrillin
marfans syndrom
mutation of fibrilin gene
lense displacement, skin joints weird
predisposint ot aortic rupture
fibronectin
cell-ECM interaction specific binding sites for matrix macromleucles and cell surface receptors dimers with repeated domains Type III binds integrin at RGD sequence needs to bind integrin to form fibril
basal lamina
ECM under epithelial cells
laminin is primary component, cross shaped, cue from cell to form sheet
type IV collagen
basal lamina functions
mechanical support compartmentalize tissue selective filter scaffold migration cell polarity
epidermolysis bullosa
defece in basmemtn membrane leading to blisters
ECM turnover
remodleing matrix metalloproteasses serine proteases regulated by local activaaiotn cell surface receptors secreted inhibtiros protease specificity
integrin receptors
heterodimerice transmembrane ECM receptors alpha and beta subunites distinct dimers short C tails and large N heads Tail link integrin to cytoskeleton head to ECM proeins
receptor mediated signaling
dynamic
inactive - bent, tighlty folded heads, tail tail contact
active - separate tails, unfolded heads
outside in signaling
ligand binds head
makes active conformation exposing binding site on tail
talin binds beta subuinit and anchors integrin to cytoskeleton
inside out signaling
talin activated binds to Beta subunit creating cross talk on surface
allosteric regulation
ligan binding make conform change on both sides so bidirectional signals
basically cuz dimers, changes in one affects both
integrin clustering
receptors in high concentratin with low affinity for ligand
velcro principle: bunhch of weak make strong
activated integrins associate laterally
focal adheison
ECM binds integrins
downstream effects, no intrinsic kinase in integrins
focal adhesion kinase
binding site revealed when talin binds integrin
FAK gets activted
growth factor receptor regulation
direct is independent because GFRs cross phosphorylate
indirect is depended