RhoB and actin polymerization coordinate Src activation with endosome-mediated delivery to the membrane

Dev Cell. 2004 Dec;7(6):855-69. doi: 10.1016/j.devcel.2004.09.019.

Abstract

We have used a c-Src-GFP fusion protein to address the spatial control of Src activation and the nature of Src-associated intracellular structures during stimulus-induced transit to the membrane. Src is activated during transit, particularly in RhoB-containing cytoplasmic endosomes associated with the perinuclear recycling compartment. Knocking out RhoB or expressing a dominant-interfering Rab11 mutant suppresses both catalytic activation of Src and translocation of active kinase to peripheral membrane structures. In addition, the Src- and RhoB-containing endosomes harbor proteins involved in actin polymerization and filament assembly, for example Scar1, and newly polymerized actin can associate with these endosomes in a Src-dependent manner. This implies that Src may regulate an endosome-associated actin nucleation activity. In keeping with this, Src controls the actin dependence of RhoB endosome movement toward the plasma membrane. This work identifies RhoB as a component of "outside-in" signaling pathways that coordinate Src activation with translocation to transmembrane receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Actins / metabolism*
  • Animals
  • Catalysis
  • Cell Adhesion
  • Cell Membrane / metabolism*
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Cytoskeleton / metabolism
  • Dose-Response Relationship, Drug
  • Endosomes / metabolism*
  • Fibronectins / metabolism
  • Genes, Dominant
  • Green Fluorescent Proteins / metabolism
  • Immunoprecipitation
  • Mice
  • Microscopy, Fluorescence
  • Plasmids / metabolism
  • Platelet-Derived Growth Factor / metabolism
  • Protein Transport
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • rab GTP-Binding Proteins / metabolism
  • rhoB GTP-Binding Protein / metabolism*
  • src-Family Kinases / metabolism*

Substances

  • Actins
  • Fibronectins
  • Platelet-Derived Growth Factor
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • src-Family Kinases
  • rab11 protein
  • rab GTP-Binding Proteins
  • rhoB GTP-Binding Protein