Ric-8 regulation of heterotrimeric G proteins

J Recept Signal Transduct Res. 2013 Jun;33(3):139-43. doi: 10.3109/10799893.2013.763828. Epub 2013 Feb 6.


Resistance to inhibitors of cholinesterase 8 proteins (Ric-8A and Ric-8B) collectively bind the four classes of heterotrimeric G protein α subunits. Ric-8A and Ric-8B act as non-receptor guanine nucleotide exchange factors (GEFs) toward the Gα subunits that each binds in vitro and seemingly regulate diverse G protein signaling systems in cells. Combined evidence from worm, fly and mammalian systems has shown that Ric-8 proteins are required to maintain proper cellular abundances of G proteins. Ric-8 proteins support G protein levels by serving as molecular chaperones that promote Gα subunit biosynthesis. In this review, the evidence that Ric-8 proteins act as non-receptor GEF activators of G proteins in signal transduction contexts will be weighed against the evidence supporting the molecular chaperoning function of Ric-8 in promoting G protein abundance. I will conclude by suggesting that Ric-8 proteins may act in either capacity in specific contexts. The field awaits additional experimentation to delineate the putative multi-functionality of Ric-8 towards G proteins in cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • GTP-Binding Protein alpha Subunits / biosynthesis
  • Gene Expression Regulation
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Mice
  • Nuclear Proteins / metabolism*
  • Protein Subunits
  • Signal Transduction


  • GTP-Binding Protein alpha Subunits
  • Guanine Nucleotide Exchange Factors
  • Nuclear Proteins
  • Protein Subunits
  • Ric8a protein, mouse
  • Heterotrimeric GTP-Binding Proteins