Rictor regulates cell migration by suppressing RhoGDI2

Oncogene. 2013 May 16;32(20):2521-6. doi: 10.1038/onc.2012.287. Epub 2012 Jul 9.

Abstract

Rictor and its binding partner Sin1 are indispensable components of mTORC2 (mammalian target of rapamycin complex 2). The mTORC2 signaling complex functions as the regulatory kinase of the distinct members of AGC kinase family known to regulate cell proliferation and survival. In the early chemotaxis studies in Dictyostelium, the rictor's ortholog has been identified as a regulator of cell migration. How rictor regulates cell migration is poorly characterized. Here we show that rictor regulates cell migration by controlling a potent inhibitor of Rho proteins known as the Rho-GDP dissociation inhibitor 2 (RhoGDI2). On the basis of on our proteomics study we identified that the rictor-dependent deficiency in cell migration is caused by upregulation of RhoGDI2 leading to a low activity of Rac and Cdc42. We found that a suppression of RhoGDI2 by rictor is not related to the Sin1 or raptor function that excludes a role of mTORC2 or mTORC1 in regulation of RhoGDI2. Our study reveals that rictor by suppressing RhoGDI2 promotes activity of the Rho proteins and cell migration.

Publication types

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

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Movement / physiology*
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Knockdown Techniques
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Mice
  • Minor Histocompatibility Antigens
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Proteins / genetics
  • Proteins / metabolism
  • Proteomics / methods
  • Rapamycin-Insensitive Companion of mTOR Protein
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Up-Regulation
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism
  • rac1 GTP-Binding Protein
  • rho Guanine Nucleotide Dissociation Inhibitor beta / genetics
  • rho Guanine Nucleotide Dissociation Inhibitor beta / metabolism*

Substances

  • ARHGDIB protein, human
  • Arhgdib protein, mouse
  • Carrier Proteins
  • Minor Histocompatibility Antigens
  • Multiprotein Complexes
  • Neuropeptides
  • Proteins
  • RICTOR protein, human
  • Rac1 protein, mouse
  • Rapamycin-Insensitive Companion of mTOR Protein
  • rho Guanine Nucleotide Dissociation Inhibitor beta
  • rictor protein, mouse
  • stress-activated protein kinase-interacting protein, mouse
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein