Membrane attachment is Key to protecting transducin GTPase-activating complex from intracellular proteolysis in photoreceptors

Sidney M. Gospe, Sheila A. Baker, Christopher Kessler, Martha F. Brucato, Joan R. Winter, Marie E Burns, Vadim Y. Arshavsky

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The members of the R7 regulator of G-protein signaling (RGS) protein subfamily are versatile regulators of G-protein signaling throughout the nervous system. Recent studies indicate that they are often found in complexes with membrane anchor proteins that serve as versatile modulators of their activity, intracellular targeting, and stability. One striking example is the interplay between the membrane anchor R9AP and the RGS9-1 · Gβ5 GTPase-activating complex responsible for the rapid inactivation of the G-protein transducin in vertebrate photoreceptor cells during their recovery from light excitation. The amount of this complex in photoreceptors sets their temporal resolution and is precisely regulated by the expression level of R9AP, which serves to protect the RGS9-1 andGβ5 subunits from intracellular proteolysis. In this study, we investigated the mechanism by which R9AP performs its protective function in mouse rods and found that it is entirely confined to recruiting RGS9-1 · Gβ5 to cellular membranes. Furthermore, membrane attachment of RGS9-1 · Gβ5 is sufficient for its stable expression in rods even in the absence of R9AP. Our second finding is that RGS9-1 · Gβ5 possesses targeting information that specifies its exclusion from the outer segment and that this information is neutralized by association with R9AP to allow outer segment targeting. Finally, we demonstrate that the ability of R9AP · RGS9-1 · Gβ5 to accelerate GTP hydrolysis on transducin is independent of its means of membrane attachment, since replacing the transmembrane domain of R9AP with a site for lipid modification did not impair the catalytic activity of this complex.

Original languageEnglish (US)
Pages (from-to)14660-14668
Number of pages9
JournalJournal of Neuroscience
Volume31
Issue number41
DOIs
StatePublished - Oct 12 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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