Control of embryonic spindle positioning and Galpha activity by C. elegans RIC-8

Curr Biol. 2004 Oct 26;14(20):1871-6. doi: 10.1016/j.cub.2004.09.059.


Asymmetric spindle positioning is of fundamental importance for generating cell diversity during development. In the C. elegans 1 cell embryo, spindle positioning has been shown to depend on heterotrimeric G protein signaling. Two Galpha subunits, GOA-1 and GPA-16 (hereafter Galpha), and receptor independent activators of G protein signaling GPR-1 and GPR-2 (GPR-1/2) are required for proper regulation of spindle positioning . However, it remains unclear whether Galpha regulates spindle positioning in its GDP or GTP bound form. Here, we investigate the role of RIC-8 in this pathway. RIC-8 was genetically shown to act in concert with goa-1 to regulate centrosome movements in C. elegans . Interestingly, mammalian RIC-8 was recently found to behave as a GEF for Galpha subunits in vitro . We show that reduction of function of ric-8 results in a 1 cell embryo phenotype very similar to the phenotype of embryos depleted of Galpha. RIC-8 is able to directly bind to GOA-1, preferentially to GOA-1-GDP, consistent with a GEF role. RIC-8 is localized at the embryo cortex, and its activity is essential for the asymmetric localization of GPR-1/2. We suggest that RIC-8 directly modulates Galpha activity and that Galpha-GTP is the signaling molecule regulating spindle positioning in the early embryo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Embryo, Nonmammalian / metabolism
  • GTP-Binding Protein alpha Subunits / metabolism*
  • Guanine Nucleotide Exchange Factors
  • Immunohistochemistry
  • Microscopy, Video
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Signal Transduction*
  • Spindle Apparatus / metabolism*
  • Two-Hybrid System Techniques


  • 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
  • RIC-8 protein, C elegans
  • GPA-16 protein, C elegans