RIAM and vinculin binding to talin are mutually exclusive and regulate adhesion assembly and turnover

Goult, Benjamin T and Zacharchenko, Thomas and Bate, Neil and Tsang, Ricky and Hey, Fiona and Gingras, Alexandre R and Elliott, Paul R and Roberts, Gordon C K and Ballestrem, Christoph and Critchley, David R and Barsukov, Igor L (2013) RIAM and vinculin binding to talin are mutually exclusive and regulate adhesion assembly and turnover. The Journal of biological chemistry, 288 (12). pp. 8238-8249. ISSN 1083-351X. (doi:https://doi.org/10.1074/jbc.M112.438119) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1074/jbc.M112.438119

Abstract

Talin activates integrins, couples them to F-actin, and recruits vinculin to focal adhesions (FAs). Here, we report the structural characterization of the talin rod: 13 helical bundles (R1-R13) organized into a compact cluster of four-helix bundles (R2-R4) within a linear chain of five-helix bundles. Nine of the bundles contain vinculin-binding sites (VBS); R2R3 are atypical, with each containing two VBS. Talin R2R3 also binds synergistically to RIAM, a Rap1 effector involved in integrin activation. Biochemical and structural data show that vinculin and RIAM binding to R2R3 is mutually exclusive. Moreover, vinculin binding requires domain unfolding, whereas RIAM binds the folded R2R3 double domain. In cells, RIAM is enriched in nascent adhesions at the leading edge whereas vinculin is enriched in FAs. We propose a model in which RIAM binding to R2R3 initially recruits talin to membranes where it activates integrins. As talin engages F-actin, force exerted on R2R3 disrupts RIAM binding and exposes the VBS, which recruit vinculin to stabilize the complex.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Ben Goult
Date Deposited: 07 Aug 2014 20:29 UTC
Last Modified: 30 Mar 2015 10:52 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/42112 (The current URI for this page, for reference purposes)
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