GMF? controls branched actin content and lamellipodial retraction in fibroblasts.

ABSTRACT: The lamellipodium is an important structure for cell migration containing branched actin nucleated via the Arp2/3 complex. The formation of branched actin is relatively well studied, but less is known about its disassembly and how this influences migration. GMF is implicated in both Arp2/3 debranching and inhibition of Arp2/3 activation. Modulation of GMF?, a ubiquitous GMF isoform, by depletion or overexpression resulted in changes in lamellipodial dynamics, branched actin content, and migration. Acute pharmacological inhibition of Arp2/3 by CK-666, coupled to quantitative live-cell imaging of the complex, showed that depletion of GMF? decreased the rate of branched actin disassembly. These data, along with mutagenesis studies, suggest that debranching (not inhibition of Arp2/3 activation) is a primary activity of GMF? in vivo. Furthermore, depletion or overexpression of GMF? disrupted the ability of cells to directionally migrate to a gradient of fibronectin (haptotaxis). These data suggest that debranching by GMF? plays an important role in branched actin regulation, lamellipodial dynamics, and directional migration.

SUBMITTER: Haynes EM 

PROVIDER: S-EPMC4477851 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature