lamellipodial extension driven by actin assembly
DESCRIPTION
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) - PowerPoint PPT PresentationTRANSCRIPT
Lamellipodial extension driven by actin assembly
Rac-GTPase
Cell spreading and migration require myosin activity
lamellipodia
lamella
Pollard T.D. and Borisy G.G., 2003, Cell, 112:453-65
Svitkina T.M. and Borisy G.G.,1999, J Cell Biol, 145:1009-26
Forces generated by Myosins?
actin plolymerization (front) and depolymarization (rear)
define the lamellipodial width
Contraction
xte io
Release
Recycling
Force Force
Attachment
Contraction
Extension
Recycling
Release
Cell migration: a cyclic process of force generation
1. lamellipodial extension:forward force exerted by actin
polymerizationon the membrane
2. extracellular matrix probing:rearward force exerted by actin flow
on integrins
How the cell locally transduces
the rigidity of the ECMinto 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
• 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.
• 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
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
Further Roles for Integrins
Steps In NC Migration
• Initiation of migration
• Migration
• Homing
• Differentiation
Rigidity of Matrix Directs Motility
Initiation of Migration
• Transition from tissue ball to migration
• Loss of cadherins
• Acquisition of Integrins
• Acquisition of motile machinery
• Stimulus to migrate
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
Matrix Forces Directed Inward And Balanced
nucleus
front
Tra
cti
on
(n
N/
m2
)
4
3
2
0
-1
-2
-3
-4
1
cell direction
time
rear tail
rear-endo-plasm
nuclearregion
ecto-plasm /lamella
front-endo-plasm
lamelli-podium
rearward
for-ward
Traction
How does a cell treat the ECM?• Movie 2: One cell deforms a collagen fibre
QuickTime™ and aVideo decompressor
are needed to see this picture.
Contraction
xte io
Release
Recycling
Force Force
Attachment
Contraction
Extension
Recycling
Release