Alpha v 3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration

Worth, Daniel C., Hodivala-Dilke, Kairbaan, Robinson, Stephen D., King, Samantha J., Morton, Penny E., Gertler, Frank B., Humphries, Martin J. and Parsons, Maddy (2010) Alpha v 3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration. Journal of Cell Biology, 189 (2). pp. 369-383. ISSN 0021-9525

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Abstract

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 ß3 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 ß3 integrin results in a loss of protein kinase A–dependent phosphorylation of the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP). Dephosphorylated VASP in ß3-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 ß1 integrin. These data demonstrate a novel mechanism by which avß3 integrin acts to locally suppress ß1 integrin activation and regulate protrusion, adhesion dynamics, and persistent migration.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Users 2731 not found.
Date Deposited: 19 Nov 2011 21:24
Last Modified: 21 Apr 2020 17:02
URI: https://ueaeprints.uea.ac.uk/id/eprint/35482
DOI: 10.1083/jcb.200912014

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