RIC-8 is required for GPR-1/2-dependent Galpha function during asymmetric division of C. elegans embryos

Cell. 2004 Oct 15;119(2):219-30. doi: 10.1016/j.cell.2004.09.026.


Heterotrimeric G proteins are crucial for asymmetric cell division, but the mechanisms of signal activation remain poorly understood. Here, we establish that the evolutionarily conserved protein RIC-8 is required for proper asymmetric division of one-cell stage C. elegans embryos. Spindle severing experiments demonstrate that RIC-8 is required for generation of substantial pulling forces on astral microtubules. RIC-8 physically interacts with GOA-1 and GPA-16, two Galpha subunits that act in a partially redundant manner in one-cell stage embryos. RIC-8 preferentially binds to GDP bound GOA-1 and is a guanine nucleotide exchange factor (GEF) for GOA-1. Our analysis suggests that RIC-8 acts before the GoLoco protein GPR-1/2 in the sequence of events leading to Galpha activation. Furthermore, coimmunoprecipitation and in vivo epistasis demonstrate that inactivation of the Gbeta subunit GPB-1 alleviates the need for RIC-8 in one-cell stage embryos. Our findings suggest a mechanism in which RIC-8 favors generation of Galpha free from Gbetagamma and enables GPR-1/2 to mediate asymmetric cell division.

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*
  • Embryo, Nonmammalian* / cytology
  • Embryo, Nonmammalian* / physiology
  • Enzyme Activation
  • Epistasis, Genetic
  • GTP-Binding Protein alpha Subunits / metabolism
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Guanine Nucleotide Dissociation Inhibitors / metabolism
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Microtubules / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • RNA Interference
  • Spindle Apparatus / metabolism
  • Stress, Mechanical
  • 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 Dissociation Inhibitors
  • Guanine Nucleotide Exchange Factors
  • Nuclear Proteins
  • RIC-8 protein, C elegans