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First published online May 6, 2009

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4 integrin: making it complex

The integrin 4β1 – which, like other integrins, spans the plasma membrane and connects cells with the extracellular matrix – is particularly important for leukocyte migration during the immune response, and defects in the 4 subunit are associated with several diseases. The 4 cytoplasmic domain is known to interact directly with the focal-adhesion protein paxillin; however, many aspects of 4-dependent migratory signalling remain unclear. Now, Martin Humphries and colleagues (p. 1654) identify a novel 4-containing signalling complex, and show how it affects known pro-migratory signalling pathways. The authors show, using FRET, that the 4 cytoplasmic domain interacts directly with 14-3-3 at adhesion contacts in CHO-B2 cells; moreover, this interaction depends on the phosphorylation of 4 at S978 (the paxillin-4 interaction depends on phosphorylation at a distinct site on 4, S988). The authors next present evidence that an 4–14-3-3–paxillin ternary complex exists in vitro and at adhesions in cells. Notably, they show that the ternary complex is required for localised activation of the pro-migration GTPase Cdc42 at the leading edge and for directed cell movement (although the association of 4 and paxillin alone is sufficient for the activation of Rac1). Their results elucidate a new mechanism of 4β1 signalling.

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An integrin-4–14-3-3–paxillin ternary complex mediates localised Cdc42 activity and accelerates cell migration

Nicholas O. Deakin, Mark D. Bass, Stacey Warwood, Julia Schoelermann, Zohreh Mostafavi-Pour, David Knight, Christoph Ballestrem, and Martin J. Humphries
JCS 2009 122: 1654-1664. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?