Sci. Signal., 22 November 2011
Vol. 4, Issue 200, p. ra79
[DOI: 10.1126/scisignal.2002223]

RESEARCH ARTICLES

Editor's Summary

Membrane Insertion Determines Function

The proteins Ric-8A (resistance to inhibitors of cholinesterase 8A) and Ric-8B are guanine nucleotide exchange factors (GEFs) that enhance signaling mediated by heterotrimeric guanine nucleotide–binding proteins (G proteins); however, whether their GEF function is required to potentiate G protein signaling has not been demonstrated. Gabay et al. derived embryonic stem cell lines from Ric-8A– or Ric-8B–deficient mice and found substantial defects in the abundance of G protein α subunits at the plasma membrane and in G protein–mediated signaling. Regulation of G protein abundance by Ric-8 proteins occurred posttranslationally. In the absence of Ric-8 proteins, G protein α subunits integrated into endomembranes poorly, resulting in decreased association with G protein β dimers and reduced heterotrimer formation. G proteins that did not associate with the membrane were rapidly degraded. Together, these data suggest that Ric-8 proteins act as chaperones for the association of G protein α subunits with endomembranes, thus controlling the biosynthesis of heterotrimeric G proteins.

Citation: M. Gabay, M. E. Pinter, F. A. Wright, P. Chan, A. J. Murphy, D. M. Valenzuela, G. D. Yancopoulos, G. G. Tall, Ric-8 Proteins Are Molecular Chaperones That Direct Nascent G Protein α Subunit Membrane Association. Sci. Signal. 4, ra79 (2011).

Read the Full Text

Dictyostelium Ric8 is a nonreceptor guanine exchange factor for heterotrimeric G proteins and is important for development and chemotaxis.

R. Kataria, X. Xu, F. Fusetti, I. Keizer-Gunnink, T. Jin, P. J. M. van Haastert, and A. Kortholt (2013)
PNAS 110, 6424-6429
 |  Abstract »  |  Full Text »  |  PDF »

Molecular chaperoning function of Ric-8 is to fold nascent heterotrimeric G protein {alpha} subunits.

P. Chan, C. J. Thomas, S. R. Sprang, and G. G. Tall (2013)
PNAS 110, 3794-3799
 |  Abstract »  |  Full Text »  |  PDF »

Regulation of the G-protein Regulatory-G{alpha}i Signaling Complex by Nonreceptor Guanine Nucleotide Exchange Factors.

S. S. Oner, E. M. Maher, M. Gabay, G. G. Tall, J. B. Blumer, and S. M. Lanier (2013)
J. Biol. Chem. 288, 3003-3015
 |  Abstract »  |  Full Text »  |  PDF »

Ric-8a, a Guanine Nucleotide Exchange Factor for Heterotrimeric G Proteins, Regulates Bergmann Glia-Basement Membrane Adhesion during Cerebellar Foliation.

S. Ma, H. J. Kwon, and Z. Huang (2012)
J. Neurosci. 32, 14979-14993
 |  Abstract »  |  Full Text »  |  PDF »

To Advertise   |   Find Products