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J Cell Biol. 2015 Jun 22;209(6):803-12. doi: 10.1083/jcb.201501094.

GMFβ controls branched actin content and lamellipodial retraction in fibroblasts.

Author information

1
UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514 Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
2
Department of Chemical & Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695.
3
UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27514 Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Howard Hughes Medical Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 jbear@email.unc.edu.

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 GMFβ, 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 GMFβ 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 GMFβ in vivo. Furthermore, depletion or overexpression of GMFβ disrupted the ability of cells to directionally migrate to a gradient of fibronectin (haptotaxis). These data suggest that debranching by GMFβ plays an important role in branched actin regulation, lamellipodial dynamics, and directional migration.

PMID:
26101216
PMCID:
PMC4477851
DOI:
10.1083/jcb.201501094
[Indexed for MEDLINE]
Free PMC Article

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