ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: Regulator of G protein signaling (RGS) proteins are GTPase-activating proteins that modulate neurotransmitter and G protein signaling. RGS7 and its binding partners Gα and Gβ5 are enriched in brain, but biochemical mechanisms governing RGS7/Gα/Gβ5 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 Gβ5 synthesized in Spodoptera frugiperda insect cells. We have found that membrane-bound but not cytosolic RGS7 is covalently modified by the fatty acid palmitate. Gβ5 is not palmitoylated. Both unmodified (cytosolic) and palmitoylated (membrane-derived) forms of RGS7, when complexed with Gβ5, are equally effective stimulators of Gαo GTPase activity, suggesting that palmitoylation does not prevent RGS7/Gαo interactions. The isolated core RGS domain of RGS7 selectively binds activated Gαi/o in brain extracts and is an effective stimulator of both Gαo and Gαi1 GTPase activities in vitro. In contrast, the RGS7/Gβ5 complex selectively interacts with Gαo only, suggesting that features outside the RGS domain and/or Gβ5 association dictate RGS7-Gα interactions. These findings define previously unrecognized biochemical properties of RGS7, including the first demonstration that RGS7 is palmitoylated.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0752103.x
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