RGS-7 completes a receptor-independent heterotrimeric G protein cycle to asymmetrically regulate mitotic spindle positioning in C. elegans

Cell. 2004 Oct 15;119(2):209-18. doi: 10.1016/j.cell.2004.09.025.

Abstract

Heterotrimeric G proteins promote microtubule forces that position mitotic spindles during asymmetric cell division in C. elegans embryos. While all previously studied G protein functions require activation by seven-transmembrane receptors, this function appears to be receptor independent. We found that mutating a regulator of G protein signaling, RGS-7, resulted in hyperasymmetric spindle movements due to decreased force on one spindle pole. RGS-7 is localized at the cell cortex, and its effects require two redundant Galphao-related G proteins and their nonreceptor activators RIC-8 and GPR-1/2. Using recombinant proteins, we found that RIC-8 stimulates GTP binding by Galphao and that the RGS domain of RGS-7 stimulates GTP hydrolysis by Galphao, demonstrating that Galphao passes through the GTP bound state during its activity cycle. While GTPase activators typically inactivate G proteins, RGS-7 instead appears to promote G protein function asymmetrically in the cell, perhaps acting as a G protein effector.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Division / physiology
  • Centrosome / metabolism
  • Embryo, Nonmammalian / anatomy & histology
  • Embryo, Nonmammalian / physiology
  • GTP-Binding Protein alpha Subunits / metabolism
  • Guanine Nucleotide Exchange Factors
  • Guanosine Triphosphate / metabolism
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Mutation
  • Nuclear Proteins / metabolism
  • Protein Binding
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • RNA Interference
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Spindle Apparatus / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • G protein regulator 1, C elegans
  • G protein regulator 2, C elegans
  • GTP-Binding Protein alpha Subunits
  • Guanine Nucleotide Exchange Factors
  • Nuclear Proteins
  • RGS Proteins
  • RIC-8 protein, C elegans
  • Recombinant Fusion Proteins
  • rgs-7 protein, C elegans
  • Guanosine Triphosphate
  • Heterotrimeric GTP-Binding Proteins