The Rif GTPase regulates cytoskeletal signaling from plexinA4 to promote neurite retraction

Neurosci Lett. 2015 Mar 17:590:178-83. doi: 10.1016/j.neulet.2015.02.010. Epub 2015 Feb 7.

Abstract

The small GTPase Rif is required for the early stages of dendritic spine formation in neurons, acting through the formin mDia2 to control actin polymerization. Rif is expressed at high levels in the brain, suggesting broader roles in neuronal function. We screened a yeast two-hybrid cDNA library to identify additional binding partners for Rif of potential relevance to neuronal function. We found that Rif interacts with FARP1, a neuronal activator of the RhoA GTPase. We show that Rif has two separate roles in FARP1 regulation-in controlling its association with plexinA4, and in releasing active RhoA from a plexinA4/FARP1 complex. The regulation of FARP1 by Rif promotes neurite retraction in cells stimulated with the semaphorin Sema6A.

Keywords: Actin; Neurite outgrowth; Plexin; Rho GTPases; Semaphorin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytoskeleton / metabolism*
  • HEK293 Cells
  • Humans
  • Jurkat Cells
  • Neurites / physiology*
  • PC12 Cells
  • Rats
  • Receptors, Cell Surface / metabolism*
  • Semaphorins / metabolism
  • Signal Transduction
  • rho GTP-Binding Proteins / metabolism*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Plxna4 protein, human
  • Receptors, Cell Surface
  • SEMA6A protein, human
  • Semaphorins
  • RHOF protein, human
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein