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Basal Lamina
a layer of extracellular matrix on which epithelium sits and which is secreted by the epithelial cells; lines the outer surface of the cell membrane; surrounds cels such as endothelial tubes, surrounds/connects muscle, fat, and schwann cells
Function: filter, barrier to cell moement; scaffolding for regeneration; highway for migration
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Proteins in the basal lamina
Type IV collagen; Laminin; Entactin; Prelecan
cells attach to the basal lamina through integrin-laminin interactions
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Laminin
- Ca2+ dependent
- 3 poolypeptides with multiple binding domains:
- beta chain: binds sulfated lipis, type IV collagen
- gamma chain: bings collagen, sulfated lipids
- alpha-helical coiled coil: binds neurites (coiled coiled chains are linked by disulfide bonds)
- LG domains: bind carbohydrates and integrins
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Prelecan
string of perals. an LG domain containing glycoprotein; assembled into sheet like multi layered network
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Collagen
single chain: alpha chain: G-X-Y motif; left handed helix: glycine packs in center; proline/hydroxyproline reuiqred for corect twist
3 makes a triple helix - right handed
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Assembly of type IV collagen
- Sheet-Forming and Anchoring Collagen
- triple helix forms in the ER: disulfides, glycosylation, hydroxylation
- after secretion: removal of propeptides; crosslinking fibrils occur extracellularly
- form dimers (tail tail C terminus) or tetramers (head head N terminus)
- form 2D network by connecting laminin in Basal Lamina
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Fibrilla Collagen Biosynthesis
- Type I, II, and III
- Made in ER: N-glycosylation, disulfide bonds, hydroxylation to form tripeptde - interact with Hsp47 to form procollagen
- trasported to golgi: lateral associaton
- secreted into ECM: propeptide cleavage: avoid polymerization at earlier steps
- Fibril assembly and crosslinking
Vitamin C and Cu2+ are important for wound healing
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Type I
Bone, Tendon, Dentinm, interact with type VI collagen
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Type II
Cartilage: chondroitin sulfate interact with type IX collagen
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Glycosaminoglycans/GAGs
Long linear polymers of speficif repeating disaccharides; usually heavily sulfated, high charged bear many - charges; highly hydrated
hyaluronan, Heparin/Heparan sulfate; chondroitin; keratan sulfate
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Proteoglycans
- a subset of glycoproteins containing covalently linked special polysaccharide chains - GGAs;
- (are glycoproteins that are heavily glycosylated)
- Proteoglyancs are super long unbranched sugars; 95% carbohydrate
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Glycoproteins
- proteins
- that contain oligosaccharide chains (glycans) covalently attached to polypeptide
- side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification.
- This process is known as glycosylation.
- In proteins that have segments extending extracellularly, the
- extracellular segments are often glycosylated. Glycoproteins are often
- important integral membrane
- proteins, where they play a role in cell-cell interactions.
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Heprain
highly sulfated glycosaminoglycan; usually stoed w/in secretory granules of most cells and released into the vasculature at sights or injury
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GAG sequence that regulates antithrombin III
- exist in heparin: sets of 5 residue sequenes in heparin bind to ATIII and activate it
- ATIII inhibits thrombin (a coagulation protein in blood stream that leads to clotting)
- activation of ATIII = inhibition of thrombin = inhibition blood clotting
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Hyaluronan
- cartilage, not sulfated, not protein linked, formed on the cell surface/PM (not golgo compared to all other GAGs!); flexible long chians; binds a lot of H2O; resists compression
- direclty secreted into ECM contributes to cell proliferation and migration (also progression of tumor)
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Aggrecan
predominant roteoglycan in cartilage; assembles with hyaluronan, into large aggregates
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Fibroblast Growth Factor (FGF)
- Growth factor invovled in angiogenesis, wound healing, and embryonic development
- Are heparin binding proteins: interactions with cell surface associated heparan sulfate proteoglycans: esseitial for FGF signal transduction
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Fibronectin
- large multi-adhesive matrix protein which binds to itself, fibrous collagens, heparin sulfate, and integrins
- Function: anchorage of cells to matrix; regulate cell shape and cytoskeleton; navigation in development and wounds
- FB expression is reduced in tumorigenic cells
binds fibrin, heparan sulfate, collagen, cell binding (RGD sequence on FN bind integrins)
RGD sequence is needed for binding
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Integrin cluster onto adhesive structures in fibroblasts
Integrins link ECM to microfilaments (adherens junction) and intermediate filaments (hemidesmosomes)
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Dystrophin glycoprotein complex (DGC)
in skeletal muscle cells
dystrophin - rod shaped cytoplasmic protein, connects the cytoskeleton of a muscle fiber to the surrounding ECM through the cell membrane
In basal lamina, laminin bind to dystroglycan form glycoprotein complex, also bind ydstrophin which binds to actin
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Leukocyte extravasation
- movement of leukocytes out of circulatory system towards the site of tissue damage/infection
- Leukocyte in its resting state: selectin ligand (leukocyte) bind to p-selectin (endothelial cell),
- Endothelial activation an leukocyte attachment and rolling: p-selectin binding on ther other side
- PAF receptor on leukocyte bind to PAF -> leukocyte activation (PAF activates integrin)
- Firm leukeocyte adhesion to endothelial cell via integrin (on leukeocye)/ICAM (on endothelia cell) binding ->both sides
- Extravasation
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