14 - 1 October 29, 2008 I ntegr in-r egulated focal...

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Unformatted text preview: 1 October 29, 2008 I ntegr in-r egulated focal adhesion kinase (FAK)-Sr c signaling and cell motility I ntegr in linked kinase (I LK) and chondr ogenesis Lectur e 14 2 (8) Oct 1 Transmembrane and FACIT collagens: skin blistering and cartilage defects Proteoglycans (1) Oct 6 Hyaruronan, aggrecan and chondrogenesis (10) Oct 8 Aggrecan and cartilage defects Perlecan: endochondral ossification and chondrodysplasia Oct 13 Thanksgiving University closed Oct 15 Term Test #1: collagens (11) Oct 20 Small leucine-rich proteoglycans (SLRPs): Decorin and collagen fibrillogenesis (12) Oct 22 Biglycan and osteogenesis Transmembrane proteoglycans: syndecan and growth factor signaling (13) Oct 27 Integrins and cell-matrix adhesion (14) Oct 29 Integrins, focal adhesion kinase (FAK) and integrin-linked kinase (ILK) 3 Light-chain phosphor ylation and the r egulation of the assembly of myosin I I into thick filaments Cell migr ation: actin-myosin contr actions Al ber ts, Molecular Biology of the Cell, 4 th Ed Fig 16-67 Also called r egulator y light chains 4 Functions of the myosin tail domain Lodish 4 th Edition Fig. 18-21 Anchor ing to plasma membr ane and vesicle tr anspor t Str ess fiber contr action + + Mechanism? 5 I ntegr in-r egulated FAK-Sr c signaling and RhoA activation Switch ON I ntegr in-r egulated FAK-Sr c complex e.g. Rho-associated Kinase (ROK) Str ess fiber assembly and focal adhesion Guanine nucleotide exchange Factor e.g. p190GEF GTPase activating pr otein (GAP) RhoA Response GDP dissociation inhibitor 6 Rho GTPase Schematic of the str uctur e of Rho GTPases and post-tr anslational modifications (RhoA, Rac1 and Cdc42) Pr enylation: membr ane inser tion signal Rho Rho is ger anylger anylated in mammals N --C H ydr ophobic tail 7 Myosin I I RLC 20 Myosin I I RLC 20 P P MLCP (active) LCK: myosin light chain kinase MLCP: myosin light chain phosphatas MLCP (inactive) P ROK (Rho-associated Kinase) RhoA Contr action Str ess fiber s Cell migr ation Activation of str ess fiber for mation and FAs by RhoA MLCK 8 Schematic of the actin cytoskeleton in a migr ating melanoma cell Small and Resch (2005) Cur r Opi nion Cell Biol 17:517, Fi g. 3 Sever ing (scissor s) Gelsolin and cofilin Myosin I I Actin contr actile assemblies gener ating later al for ces Ar c-like ar r ays (ar ) Lamellipodium (lp) pushing for ce Contr actile per ipher al bundles Focal adhesion site Micr ospike bundle Dir ection of migr ation 9 Dr amatic effects of Rac, Rho and Cdc42 on actin or ganization in fibr oblasts 10 A moving cell exer ts tr action for ces on the substr atum A ker atinocyte plated on a thin silicon membr ane exer ts later al for ces fr om contr action of the cell body,...
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14 - 1 October 29, 2008 I ntegr in-r egulated focal...

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