Lamellipodial extension driven by actin assembly
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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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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)

define the lamellipodial width

Forces generated by Myosins?

Cell spreading and migration require myosin activity


Lamellipodial extension driven by actin assembly

Release

Extension

Contraction

Attachment

Recycling

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Lamellipodial extension driven by actin assembly

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


Neural crest migration

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.


Lamellipodial extension driven by actin assembly

  • 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.


Extracellular matrix integrin interactions in motility and signaling

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


Integrin knockouts have severe phenotypes

Integrin Knockouts have Severe Phenotypes


Further roles for integrins

Further Roles for Integrins


Steps in nc migration

Steps In NC Migration

  • Initiation of migration

  • Migration

  • Homing

  • Differentiation


Rigidity of matrix directs motility

Rigidity of Matrix Directs Motility


Initiation of migration

Initiation of Migration

  • Transition from tissue ball to migration

  • Loss of cadherins

  • Acquisition of Integrins

  • Acquisition of motile machinery

  • Stimulus to migrate


Lamellipodial extension driven by actin assembly

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


Attachment and contraction

Attachment and Contraction


Lamellipodial extension driven by actin assembly

Matrix Forces Directed

Inward And Balanced

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How does a cell treat the ecm

How does a cell treat the ECM?

  • Movie 2: One cell deforms a collagen fibre


Lamellipodial extension driven by actin assembly

Release

Extension

Contraction

Attachment

Recycling

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