Expression and localization of RGS9-2/Gβ5/R7BP complex in vivo is set by dynamic control of its constitutive degradation by cellular cysteine proteases

Garret R. Anderson, Rafael Lujan, Arthur Semenov, Marco Pravetoni, Ekaterina N. Posokhova, Joseph H. Song, Vladimir Uversky, Ching Kang Chen, Kevin Wickman, Kirill A. Martemyanov

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

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 β subunit/R7BP complexes at postsynaptic sites in unison with increased signaling demands at mature synapses.

Original languageEnglish (US)
Pages (from-to)14117-14127
Number of pages11
JournalJournal of Neuroscience
Volume27
Issue number51
DOIs
StatePublished - Dec 19 2007

Keywords

  • G-protein
  • Intracellular targeting
  • Protein degradation
  • RGS proteins
  • Signal transduction
  • Striatum

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