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Lamellipodial extension driven by actin assembly

Lamellipodial extension driven by actin assembly. Rac-GTPase. lamellipodia. lamella. Svitkina T.M. and Borisy G.G., 1999, J Cell Biol, 145:1009-26. Pollard T.D. and Borisy G.G., 2003, Cell, 112:453-65. actin plolymerization (front) and depolymarization (rear)

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Lamellipodial extension driven by actin assembly

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  1. Lamellipodial extension driven by actin assembly Rac-GTPase lamellipodia lamella Svitkina T.M. and Borisy G.G., 1999, J Cell Biol, 145:1009-26 Pollard T.D. and Borisy G.G., 2003, Cell, 112:453-65 actin plolymerization (front) and depolymarization (rear) define the lamellipodial width Forces generated by Myosins? Cell spreading and migration require myosin activity

  2. Release Extension Contraction Attachment Recycling x t e i o C o n t r a c t i o n F o r c e F o r c e R e l e a s e R e c y c l i n g

  3. Cell migration: a cyclic process of force generation 1. lamellipodial extension: forward force exerted by actin polymerization on the membrane 2. extracellular matrix probing: rearward force exerted by actin flow on integrins How the cell locally transduces the rigidity of the ECM into a contractile signal used to direct lamellipodial extension? Sheetz M.P., Felsenfeld D.P., Galbraith C.G., 1998, Trends Cell Biol, 8:51-4

  4. Neural Crest Migration • The peripheral nervous system is created by a spatiotemporally co-ordinated migratory process during which the precursor cells, the neural crest (NC) cells, traverse the embryo to reach distantly located sites.

  5. Homing of peripheral neurons and their supportive cells might be dictated by a delicate equilibrium between the multiple actions of stimulatory and inhibitory molecules, which is modulated further by defined responses of the dispersing cells to these ECM components during their successive phases of phenotypic diversification.

  6. Extracellular Matrix-Integrin Interactions in Motility and Signaling Matrix molecules are typically bound by integrins Integrins are alpha-beta dimeric membrane proteins needed for motility, signal, and force transduction. Antibodies to integrins block cell migration and spreading

  7. Integrin Knockouts have Severe Phenotypes

  8. Further Roles for Integrins

  9. Steps In NC Migration • Initiation of migration • Migration • Homing • Differentiation

  10. Rigidity of Matrix Directs Motility

  11. Initiation of Migration • Transition from tissue ball to migration • Loss of cadherins • Acquisition of Integrins • Acquisition of motile machinery • Stimulus to migrate

  12. Important Aspects of Migration 1. Isovolumic 2. Constant Membrane Area 3. Actin filament assembly and disassembly 4. Actin filament contraction 5. Matrix binding 6. Matrix Rigidity 7. Release of matrix binding

  13. Attachment and Contraction

  14. Matrix Forces Directed Inward And Balanced time 4 c e l l d i r e c t i o n rear 3 ) 2 m 2 n u c l e u s m / 1 N f r o n t n ( 0 n o i t c - 1 a r T - 2 - 3 - 4

  15. How does a cell treat the ECM? • Movie 2: One cell deforms a collagen fibre

  16. Release Extension Contraction Attachment Recycling x t e i o C o n t r a c t i o n F o r c e F o r c e R e l e a s e R e c y c l i n g

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