Expression and localization of RGS9-2/G 5/R7BP complex in vivo is set by dynamic control of its constitutive degradation by cellular cysteine proteases

J Neurosci. 2007 Dec 19;27(51):14117-27. doi: 10.1523/JNEUROSCI.3884-07.2007.


A member of regulator of G-protein signaling family, RGS9-2, is an essential modulator of signaling through neuronal dopamine and opioid G-protein-coupled receptors. Recent findings indicate that the abundance of RGS9-2 determines sensitivity of signaling in the locomotor and reward systems in the striatum. In this study we report the mechanism that sets the concentration of RGS9-2 in vivo, thus controlling G-protein signaling sensitivity in the region. We found that RGS9-2 possesses specific degradation determinants which target it for constitutive destruction by lysosomal cysteine proteases. Shielding of these determinants by the binding partner R7 binding-protein (R7BP) controls RGS9-2 expression at the posttranslational level. In addition, binding to R7BP in neurons targets RGS9-2 to the specific intracellular compartment, the postsynaptic density. Implementation of this mechanism throughout ontogenetic development ensures expression of RGS9-2/type 5 G-protein beta subunit/R7BP complexes at postsynaptic sites in unison with increased signaling demands at mature synapses.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Membrane / chemistry
  • Cell Membrane / enzymology*
  • Cell Membrane / genetics
  • Corpus Striatum / chemistry
  • Corpus Striatum / metabolism
  • Cysteine Endopeptidases / analysis
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / physiology*
  • Gene Expression Regulation, Enzymologic / physiology*
  • Lysosomes / enzymology
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • RGS Proteins / biosynthesis*
  • RGS Proteins / genetics
  • RGS Proteins / metabolism


  • R7BP protein, mouse
  • RGS Proteins
  • regulator of g-protein signaling 9
  • Cysteine Endopeptidases