The integrin α4β1 – 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 α4 subunit are associated with several diseases. The α4 cytoplasmic domain is known to interact directly with the focal-adhesion protein paxillin; however, many aspects of α4-dependent migratory signalling remain unclear. Now, Martin Humphries and colleagues (p. 1654) identify a novel α4-containing signalling complex, and show how it affects known pro-migratory signalling pathways. The authors show, using FRET, that the α4 cytoplasmic domain interacts directly with 14-3-3ζ at adhesion contacts in CHO-B2 cells; moreover, this interaction depends on the phosphorylation of α4 at S978 (the paxillin-α4 interaction depends on phosphorylation at a distinct site on α4, S988). The authors next present evidence that an α4–14-3-3ζ–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 α4 and paxillin alone is sufficient for the activation of Rac1). Their results elucidate a new mechanism of α4β1 signalling.
α4 integrin: making it complex
α4 integrin: making it complex. J Cell Sci 15 May 2009; 122 (10): e1005. doi:
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