GMFβ controls branched actin content and lamellipodial retraction in fibroblasts

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / antagonists & inhibitors
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / biosynthesis*
  • Animals
  • Cell Line
  • Cell Movement / physiology*
  • Enzyme Activation
  • Fibroblasts / physiology
  • Fibronectins / pharmacology
  • Glia Maturation Factor / physiology*
  • Indoles / pharmacology
  • Mice
  • Protein Isoforms / biosynthesis
  • Pseudopodia / physiology*


  • Actin-Related Protein 2-3 Complex
  • Actins
  • CK-0944666
  • Fibronectins
  • Glia Maturation Factor
  • Indoles
  • Protein Isoforms