Coronin 1A promotes a cytoskeletal-based feedback loop that facilitates Rac1 translocation and activation

EMBO J. 2011 Aug 26;30(19):3913-27. doi: 10.1038/emboj.2011.310.

Abstract

The activation of the Rac1 GTPase during cell signalling entails its translocation from the cytosol to membranes, release from sequestering Rho GDP dissociation inhibitors (RhoGDI), and GDP/GTP exchange. In addition to those steps, we show here that optimal Rac1 activation during cell signalling requires the engagement of a downstream, cytoskeletal-based feedback loop nucleated around the cytoskeletal protein coronin 1A and the Rac1 exchange factor ArhGEF7. These two proteins form a cytosolic complex that, upon Rac1-driven F-actin polymerization, translocates to juxtamembrane areas where it expands the pool of activated, membrane-bound Rac1. Such activity requires the formation of an F-actin/ArhGEF7-dependent physical complex of coronin 1A with Pak1 and RhoGDIα that, once assembled, promotes the Pak1-dependent dissociation of Rac1 from the Rac1/RhoGDIα complex and subsequent Rac1 activation. Genetic evidence demonstrates that this relay circuit is essential for generating sustained Rac1 activation levels during cell signalling.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Cytoskeleton / metabolism*
  • Cytosol / metabolism
  • Gene Expression Regulation*
  • Green Fluorescent Proteins / metabolism
  • Guanine Nucleotide Dissociation Inhibitors / metabolism
  • Kinetics
  • Microfilament Proteins / metabolism*
  • Models, Biological
  • Protein Transport
  • Signal Transduction
  • rac1 GTP-Binding Protein / metabolism*
  • rho Guanine Nucleotide Dissociation Inhibitor alpha
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors

Substances

  • ARHGDIA protein, human
  • Actins
  • Guanine Nucleotide Dissociation Inhibitors
  • Microfilament Proteins
  • RAC1 protein, human
  • rho Guanine Nucleotide Dissociation Inhibitor alpha
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors
  • coronin proteins
  • Green Fluorescent Proteins
  • rac1 GTP-Binding Protein