320Fall09Lecture23

320Fall09Lecture23 - BIO 320 Cell Biology, Fall 09 Dr....

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BIO 320 Cell Biology, Fall ‘09 Dr. Thomas Bushart Lecture 23
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Topics Integrins Extracellular matrix – connective tissues Principles of cell signalling
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Integrins Transmembrane, cell-matrix adhesion receptors Cell adhesion Linkage between ECM and (mostly) actin network May be transient and weak, or strong and long lasting Signaling (“matrix receptors”) Matrix binding can activate signaling pathways Internal signals can modulate binding
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Integrin structure Heterodimers of α and β subunits ( α n β n) β 2 is found only on white blood cells, for example In hemidesmosomes connect basal lamina to keratin filaments ( α 6 β 4) Internal and external binding are both key to functionality
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Integrin changes Motile cells need control over their attachments Allosteric regulation Ligand binding stimulates internal binding
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“Inside-out activation”
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Adhesions and signaling Focal adhesions and other structures can lead to broad signaling or localized changes
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Integrin adhesions Recruited clustering strengthens attachments Actin-based focal adhesions Rho (small GTPase) promotes actin filament and integrin recruitment Hemidesmosomes Promote cell survival and cell proliferation Anchorage dependence Loss of contact with ECM for some cells will lead to apoptosis
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Cell growth and survival
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The extracellular matrix (ECM) The other extreme of cell contacts is exemplified by connective tissues
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ECM Specialized cells (fibroblasts) produce and organize the ECM Glycosaminoglycans (GAGs) Polysaccharide chains Linked to form proteoglycans Fibrous proteins Structural and adhesion points Collagen, elastin, fibronectin, laminin
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GAGs Hyaluronan; chondroitin sulfate and dermatin sulfate; heparan sulfate; keratan sulfate Gel forming properties Polysaccharides cannot fold up like proteins Negative charges attract counter ions Attracts large amounts of water Turgor resists compressive forces
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Proteoglycans Contain at least one GAG Unbranched Typically more carbohybrate than protein Highly variable, even in same type Glycoprotein properties are opposite Proteoglycans Glycoprotein
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GAG organization in the ECM Can associate with other GAGs Aggrecan on hyaluronan Associate with the fibrous ECM proteins
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Proteoglycan functions Hydrating gels Molecular sieves Perlecan in the basal lamina of kidneys Binding of secreted proteins Anchoring, inhibiting, storing, presentation Chemokines are immobilized on blood vessel endothelial cells for presentation to white blood cells
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Collagens Fibrous proteins in all
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This note was uploaded on 01/25/2010 for the course BIO 51055 taught by Professor Bushart during the Fall '09 term at University of Texas.

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320Fall09Lecture23 - BIO 320 Cell Biology, Fall 09 Dr....

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