Hankenson #2 - ExtracellularMatrix...

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Extracellular Matrix Kurt D. Hankenson, D.V.M., Ph.D. Orthopaedic Research Laboratories [email protected]
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Extracellular Matrix DAY 1 DAY 1 Generalized overview Generalized overview Collagens Collagens DAY 2 Elastin Elastin Proteoglycans Matricellular proteins Adhesive proteins Extracellular enzymes DAY 3 Cell adhesion Mechanical transduction Specialized structures
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Extracellular Matrix Collagen review triple helix 3 alpha chains Gly-X-Y Fibrillar collagen secreted as procollagen molecules fibrils organized into fibers Enzymes for processing
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Extracellular Matrix Elastin
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Extracellular Matrix Elastin Confers resilience » Stretch/relaxation » Analogous to a rubber band Tissues such as skin, blood vessels, and lungs » Elastic fibers
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Extracellular Matrix Elastin Elastin domains contain building blocks of GX, PX, GGX, PGX, where X=G,A,V,L,I » What is significant about those amino acids?
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Extracellular Matrix Elastin Elastin domains contain building blocks of GX, PX, GGX, PGX, where X=G,A,V,L,I » What is significant about those amino acids, and what they can promote? Highly hydrophobic - aggregation!!
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Extracellular Matrix Elastin Secreted as tropoelastin tropoelastin crosslinked in large macromolecular aggregates by lysyl oxidase
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Extracellular Matrix Similar to lysyl oxidase, what was an extracellular enzyme mentioned in the 1 st lecture, and what was its purpose?
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Extracellular Matrix Similar to lysyl oxidase, what was an extracellular enzyme mentioned in the 1 st lecture, and what was its purpose? Procollagen peptidase » (protein name is ADAM-TS)
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Extracellular Matrix Fibrillin Essential component of elastin morphogenesis and function Two genes (1 and 2) – very similar Multifunctional
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Extracellular Matrix Fibrillin » Formation of microfibrils “beaded string” » Microfibrils act to orient elastin into fibers » or provide microfibrilar networks » Provide constraint to ‘over elasticity’
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Dog aorta Elastic fibers
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Extracellular Matrix Fibrillin » Mutations in fibrillin genes result in Marfan Syndrome Hyperelasticity Developmental defects Increased body length Lengthening of facial structural Adult abnormalities Over elastic skin and vasculature
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  • Winter '08
  • HUNT
  • Collagen, Glycosaminoglycan, Hyaluronan, dermatan sulfate, III III III III III III

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