Article abstract

Nature Cell Biology 9, 1046 - 1056 (2007)
Published online: 26 August 2007 | doi:10.1038/ncb1626

Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex

Bryan Serrels1, Alan Serrels1, Valerie G. Brunton1, Mark Holt2, Gordon W. McLean1,3, Christopher H. Gray1, Gareth E. Jones2 & Margaret C. Frame1

Networks of actin filaments, controlled by the Arp2/3 complex, drive membrane protrusion during cell migration. How integrins signal to the Arp2/3 complex is not well understood. Here, we show that focal adhesion kinase (FAK) and the Arp2/3 complex associate and colocalize at transient structures formed early after adhesion. Nascent lamellipodia, which originate at these structures, do not form in FAK-deficient cells, or in cells in which FAK mutants cannot be autophosphorylated after integrin engagement. The FERM domain of FAK binds directly to Arp3 and can enhance Arp2/3-dependent actin polymerization. Critically, Arp2/3 is not bound when FAK is phosphorylated on Tyr 397. Interfering peptides and FERM-domain point mutants show that FAK binding to Arp2/3 controls protrusive lamellipodia formation and cell spreading. This establishes a new function for the FAK FERM domain in forming a phosphorylation-regulated complex with Arp2/3, linking integrin signalling directly with the actin polymerization machinery.

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  1. The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
  2. Randall Division of Cell & Molecular Biophysics, King's College London, Guy's Campus, London SE1 1UL, UK.
  3. Current address: Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4SA, UK.

Correspondence to: Margaret C. Frame1 e-mail: m.frame@beatson.gla.ac.uk



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