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

B Serrels, A Serrels, VG Brunton, M Holt… - Nature cell …, 2007 - nature.com
B Serrels, A Serrels, VG Brunton, M Holt, GW McLean, CH Gray, GE Jones, MC Frame
Nature cell biology, 2007nature.com
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 …
Abstract
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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