Sci. Signal., 22 November 2011
Membrane Insertion Determines FunctionThe 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).
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