What makes up the ECM?
glycoproteins (big proteins with small sugars)
proteoglycans (small proteins with big sugars)
elastic fibers
Laminin
heterotrimeric complex that can bind to integrin
Collagen
glycoprotein
provides tensile strength
binds to fibronectin
three types: fibrilllar, sheet forming, anchoring
Fibrillar collagen
- glycoprotein found in bone, eye, tendons, dense CT
- made in the ER, Lys and Pro are hydroxylated, hydroxylysine is glycosylated, assembles into 3 alpha chains. Is then secreted into cell, the pro-domains are cleaved and fibrils are formed
Sheet-forming collagen
glycoprotein found in the basal lamina
Fibronectin
glycoprotein binds to collagen then to integrin
Nidrogens
glycoprotein linker protein
Perlecan
type of proteoglycan
Aggrecan
proteoglycan found in the inside of cartilarge ECM
helps activate fibroblast growth factor
inhibits TGF-beta
Syndecan
proteoglycan found embedded in the PM on fibroblasts
interacts with fibronectin
Betacan
proteoglycan found embedded in the PM, helps activate TGF-beta signaling
Elastic fibers
allow for stretching
found in ECM of CT, blood vessels, skin and lungs
Elastin
type of elastic fiber that finds TGF-beta and prevents it from binding to receptor
Microfibrils
polymers composed of fibrillin (mutated in Marfan’s)
Matrix Metalloproteins
degrade ECM and require Ca and Zn
Regulation of MMPs
1) local activation - secrete as inactive precursor
Ex. plasminogen -> cleaved to be plasmin which break up blood clots
2) confinement by cell surface receptors: inactive protease bind receptors and confine them
Ex. non-mutated uPA ninds to receptor and degrades the ECM, mutated uPA binds to the receptor and inhibits degradation (block cancer cells)
3) secretion of inhibitors: controlled by local MMPs
Ex. TIMP’s bind to active MMPs and inactivates it protecting the ECM
Leukocyte extravasation
1) macrophage in damaged tissue releases cytokines to attract leukocytes
2) selectin expression induced on endothelial cells lining the blood vessel
3) carbohydrates on leukocytes weakly bind to selectins
4) integrins on leukocytes bind ICAM’s on endothelial cells
5) leukocytes pass through gaps mediated by PECAM’s
Tight junctions (zonula occludens)
- located on the apical, lateral domain
- uses claudins and occludens that connect to actin
- forms a protective barrier that forces stuff to pass through the cell
- forms a functional barrier that maintains polarity
Adherens junctions (zonula adherens)
- lateral domain
- cadherins and catenins that connect to actin
- hold the cell together by connecting to actin
Desmosomes (macula adherens)
- lateral domain
- cadherins: desmoglein and desmocollins
- plaque made by plakoglobin and desmoplakin
- provide mechanical strength by linking plaques to intermediate filaments (keratin)
Hemidesmosomes
- basal domain
- integrins (type IV and laminin)
- plaques made of dystonin and plecin
- attaches cell to basal lamina via keratin
Gap junctions
- connects adjacent cells
- made of connexin (forms connexons)
- allows passage of small ions and electrical waves of excitation
