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

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dc.contributor.author Gertler, Frank
dc.contributor.author Worth, Daniel C.
dc.contributor.author Hodivala-Dilke, Kairbaan
dc.contributor.author Robinson, Stephen D.
dc.contributor.author King, Samantha J.
dc.contributor.author Morton, Penny E.
dc.contributor.author Humphries, Martin J.
dc.contributor.author Parsons, Maddy
dc.date.accessioned 2011-02-11T22:24:35Z
dc.date.available 2011-02-11T22:24:35Z
dc.date.issued 2010-04
dc.identifier.issn 0021-9525
dc.identifier.issn 1540-8140
dc.identifier.uri http://hdl.handle.net/1721.1/60934
dc.description.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 β3 [beta 3] 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 [beta 3] integrin results in a loss of protein kinase A–dependent phosphorylation of the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP). Dephosphorylated VASP in β3 [beta 3]-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 [beta 1] integrin. These data demonstrate a novel mechanism by which αvβ3 [alpha nu beta 3]integrin acts to locally suppress β1 [beta 1]integrin activation and regulate protrusion, adhesion dynamics, and persistent migration. en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant GM50081) en_US
dc.language.iso en_US
dc.publisher Rockefeller University Press en_US
dc.relation.isversionof http://dx.doi.org/10.1083/jcb.200912014 en_US
dc.rights Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. en_US
dc.source Rockefeller UP en_US
dc.title αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration en_US
dc.title.alternative αvβ3 [alpha nu beta 3] integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration en_US
dc.type Article en_US
dc.identifier.citation Worth, D. C. et al. "αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration.” The Journal of Cell Biology 189.2 (2010): 369-383. en_US
dc.contributor.department David H. Koch Institute for Integrative Cancer Research at MIT en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Biology en_US
dc.contributor.approver Gertler, Frank
dc.contributor.mitauthor Gertler, Frank
dc.relation.journal Journal of Cell Biology en_US
dc.identifier.mitlicense PUBLISHER_POLICY en_US
dc.eprint.version Final published version en_US
dc.type.uri http://purl.org/eprint/type/JournalArticle en_US
eprint.status http://purl.org/eprint/status/PeerReviewed en_US
dspace.orderedauthors Worth, D. C.; Hodivala-Dilke, K.; Robinson, S. D.; King, S. J.; Morton, P. E.; Gertler, F. B.; Humphries, M. J.; Parsons, M. en


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