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The Extracellular Matrix Michael Malahy
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ECM in Epithelial Sheets 3 types of molecules abundant in ECM Proteoglycans Cushion cells and bind extracellular molecules Collagen Mechanical strength and resilience Multiadhesive Matrix Proteins Bind and cross-link adhesion receptors and other ECM components
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Basal Lamina Type IV Collagen Trimeric, rod-like and globular, 2D Laminins Multiadhesive proteins that form 2D network with collagen and bind integrins Entactin Rod-like, cross-link collagen and laminin and helps incorporate other ECM components Perlecan Multidomain proteoglycan, binds and cross-links ECM components and cell-surface molecules
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Type IV Collagen Trimeric Collagen α chains Homo- or heterotrimeric 1 or more 3-stranded segments Each strand is left-handed 3 strands twisted right-handed Glycine, Proline and Hydroxyproline Unusual abundance Gly-X-Y Lysine and Hydroxylysine
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Figure 6.14
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Figure 6.16
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Proteoglycans Membrane associated or secreted core proteins covalently linked to GAG chains Glycosaminoglycans (GAG) Sulfated Disaccharides Syndecans Cell-surface Bind collagen, fibronectin and external signaling molecules such as growth factors Regulate cellular metabolism and function
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Fibrillar Collagens Produced largely by Fibroblasts Trimeric Type I Collagen Polymers Fibrils Larger bundles Fibers Form tendons Gram for gram higher tensile strength than steel
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Fibronectin Multiadhesive matrix protein All isoforms from alternative splicing of RNA from a single gene Essential for migration differentiation in embryogenesis Promote blood clotting and facilitate migration of immune cells to a wound Attach cells to ECM by binding fibrous collagen and heparan sulfate proteoglycans to cell-surface adhesion receptors such as integrins
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Fibronectins cont’d Influence shape and movement of cells Influence organization of the cytoskeleton Dimer of 2 similar polypeptides 6 functional regions with ligand-binding specificities Each region contains certain repeating sequences Type I, II or III Beads on a string Arg-Gly-Asp RGD sequence recognizes several integrins
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