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R egulator of G protein s ignaling (RGS) proteins are GTPase-activating proteins that modulate neurotransmitter and G protein signaling. RGS7 and its binding partners G[alpha] and G[beta]5 are enriched in brain, but biochemical mechanisms governing RGS7/G[alpha]/G[beta]5 interactions and membrane association are poorly defined. We report that RGS7 exists as one cytosolic and three biochemically distinct membrane-bound fractions (salt-extractable, detergent-extractable, and detergent-insensitive) in brain. To define factors that determine RGS7 membrane attachment, we examined the biochemical properties of recombinant RGS7 and G[beta]5 synthesized in Spodoptera frugiperda insect cells. We have found that membrane-bound but not cytosolic RGS7 is covalently modified by the fatty acid palmitate. G[beta]5 is not palmitoylated. Both unmodified (cytosolic) and palmitoylated (membrane-derived) forms of RGS7, when complexed with G[beta]5, are equally effective stimulators of G[alpha]o GTPase activity, suggesting that palmitoylation does not prevent RGS7/G[alpha]o interactions. The isolated core RGS domain of RGS7 selectively binds activated G[alpha]i/o in brain extracts and is an effective stimulator of both G[alpha]o and G[alpha]i1 GTPase activities in vitro. In contrast, the RGS7/G[beta]5 complex selectively interacts with G[alpha]o only, suggesting that features outside the RGS domain and/or G[beta]5 association dictate RGS7-G[alpha] interactions. These findings define previously unrecognized biochemical properties of RGS7, including the first demonstration that RGS7 is palmitoylated.

(C) 2000 International Society for Neurochemistry