Current Biology
Volume 22, Issue 16, 21 August 2012, Pages 1510-1515
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Exo70 Stimulates the Arp2/3 Complex for Lamellipodia Formation and Directional Cell Migration

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Summary

Directional cell migration requires the coordination of actin assembly and membrane remodeling. The exocyst is an octameric protein complex essential for exocytosis and plasma membrane remodeling [1, 2]. A component of the exocyst, Exo70, directly interacts with the Arp2/3 complex, a core nucleating factor for the generation of branched actin networks for cell morphogenesis and migration [3, 4, 5, 6, 7, 8, 9]. Using in vitro actin polymerization assay and time-lapse total internal reflection fluorescence microscopy, we found that Exo70 functions as a kinetic activator of the Arp2/3 complex that promotes actin filament nucleation and branching. We further found that the effect of Exo70 on actin is mediated by promoting the interaction of the Arp2/3 complex with WAVE2, a member of the N-WASP/WAVE family of nucleation promoting factors. At the cellular level, the stimulatory effect of Exo70 on the Arp2/3 complex is required for lamellipodia formation and maintaining directional persistence of cell migration. Our findings provide a novel mechanism for regulating actin polymerization and branching for effective membrane protrusion during cell morphogenesis and migration.

Highlights

► Exo70 kinetically stimulates the Arp2/3 complex-mediated actin assembly ► The Exo70-ARPC1 interaction is required for stimulating the Arp2/3 complex ► Exo70 promotes the interaction between the Arp2/3 complex and WAVE2 ► The Exo70-Arp2/3 interaction regulates lamellipodia formation and cell migration

Cited by (0)

4

These authors contributed equally to this work

5

Present address: Biodynamic Optical Imaging Center, Peking University, Beijing 100871, China

6

Present address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA