Extra Cellular Matrix

  1. 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
  2. Proteins in the basal lamina
    Type IV collagen; Laminin; Entactin; Prelecan

    cells attach to the basal lamina through integrin-laminin interactions
  3. 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
  4. Prelecan
    string of perals. an LG domain containing glycoprotein; assembled into sheet like multi layered network
  5. 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
  6. 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
  7. 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
  8. Type I
    Bone, Tendon, Dentinm, interact with type VI collagen
  9. Type II
    Cartilage: chondroitin sulfate interact with type IX collagen
  10. 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
  11. 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
  12. 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.
  13. Heprain
    highly sulfated glycosaminoglycan; usually stoed w/in secretory granules of most cells and released into the vasculature at sights or injury
  14. 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
  15. 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)
  16. Aggrecan
    predominant roteoglycan in cartilage; assembles with hyaluronan, into large aggregates
  17. 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
  18. 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
  19. Integrin cluster onto adhesive structures in fibroblasts
    Integrins link ECM to microfilaments (adherens junction) and intermediate filaments (hemidesmosomes)
  20. 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
  21. 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
Card Set
Extra Cellular Matrix