RGS7 is palmitoylated and exists as biochemically distinct forms

J Neurochem. 2000 Nov;75(5):2103-12. doi: 10.1046/j.1471-4159.2000.0752103.x.


Regulator of G protein signaling (RGS) proteins are GTPase-activating proteins that modulate neurotransmitter and G protein signaling. RGS7 and its binding partners Galpha and Gbeta5 are enriched in brain, but biochemical mechanisms governing RGS7/Galpha/Gbeta5 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 Gbeta5 synthesized in Spodoptera frugiperda insect cells. We have found that membrane-bound but not cytosolic RGS7 is covalently modified by the fatty acid palmitate. Gbeta5 is not palmitoylated. Both unmodified (cytosolic) and palmitoylated (membrane-derived) forms of RGS7, when complexed with Gbeta5, are equally effective stimulators of Galpha(o) GTPase activity, suggesting that palmitoylation does not prevent RGS7/Galpha(o) interactions. The isolated core RGS domain of RGS7 selectively binds activated Galpha(i/o) in brain extracts and is an effective stimulator of both Galpha(o) and Galpha(i1) GTPase activities in vitro. In contrast, the RGS7/Gbeta5 complex selectively interacts with Galpha(o) only, suggesting that features outside the RGS domain and/or Gbeta5 association dictate RGS7-Galpha interactions. These findings define previously unrecognized biochemical properties of RGS7, including the first demonstration that RGS7 is palmitoylated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain Chemistry
  • Cattle
  • Cell Line
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Detergents / chemistry
  • Dimerization
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein beta Subunits*
  • GTP-Binding Proteins / chemistry*
  • Guanosine Triphosphate / metabolism
  • Heterotrimeric GTP-Binding Proteins / chemistry
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Isoenzymes / chemistry
  • Palmitic Acid / chemistry*
  • Phospholipase C beta
  • Protein Structure, Tertiary
  • RGS Proteins / chemistry*
  • RGS Proteins / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Spodoptera
  • Type C Phospholipases / chemistry


  • Detergents
  • GTP-Binding Protein beta Subunits
  • Gnb5 protein, rat
  • Isoenzymes
  • RGS Proteins
  • Recombinant Proteins
  • Rgs7 protein, mouse
  • Palmitic Acid
  • Guanosine Triphosphate
  • Type C Phospholipases
  • Phospholipase C beta
  • GTP-Binding Proteins
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Heterotrimeric GTP-Binding Proteins