αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration

Integrins are fundamental to the control of protrusion and motility in adherent cells. However, the mechanisms by which specific members of this receptor family cooperate in signaling to cytoskeletal and adhesion dynamics are poorly understood. Here, we show that the loss of β3 integrin in fibroblas...

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Bibliographic Details
Published in:The Journal of cell biology 2010-04, Vol.189 (2), p.369-383
Main Authors: Worth, Daniel C, Hodivala-Dilke, Kairbaan, Robinson, Stephen D, King, Samantha J, Morton, Penny E, Gertler, Frank B, Humphries, Martin J, Parsons, Maddy
Format: Article
Language:English
Subjects:
Actins
Cell adhesion
Cell lines
Fibroblasts
Fibrosis
Focal adhesions
Integrins
Phosphorylation
Physiological regulation
Quantification
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Summary:Integrins are fundamental to the control of protrusion and motility in adherent cells. However, the mechanisms by which specific members of this receptor family cooperate in signaling to cytoskeletal and adhesion dynamics are poorly understood. Here, we show that the loss of β3 integrin in fibroblasts results in enhanced focal adhesion turnover and migration speed but impaired directional motility on both 2D and 3D matrices. These motility defects are coupled with an increased rate of actin-based protrusion. Analysis of downstream signaling events reveals that loss of β3 integrin results in a loss of protein kinase A-dependent phosphorylation of the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP). Dephosphorylated VASP in β3-null cells is preferentially associated with Rap1-GTP-interacting adaptor molecule (RIAM) both in vitro and in vivo, which leads to enhanced formation of a VASP-RIAM complex at focal adhesions and subsequent increased binding of talin to β1 integrin. These data demonstrate a novel mechanism by which αvβ3 integrin acts to locally suppress β1 integrin activation and regulate protrusion, adhesion dynamics, and persistent migration.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200912014