Changes in striatal signaling induce remodeling of RGS complexes containing Gbeta5 and R7BP subunits

Mol Cell Biol. 2009 Jun;29(11):3033-44. doi: 10.1128/MCB.01449-08. Epub 2009 Mar 30.


Neurotransmitter signaling via G protein coupled receptors is crucially controlled by regulators of G protein signaling (RGS) proteins that shape the duration and extent of the cellular response. In the striatum, members of the R7 family of RGS proteins modulate signaling via D2 dopamine and mu-opioid receptors controlling reward processing and locomotor coordination. Recent findings have established that R7 RGS proteins function as macromolecular complexes with two subunits: type 5 G protein beta (Gbeta5) and R7 binding protein (R7BP). In this study, we report that the subunit compositions of these complexes in striatum undergo remodeling upon changes in neuronal activity. We found that under normal conditions two equally abundant striatal R7 RGS proteins, RGS9-2 and RGS7, are unequally coupled to the R7BP subunit, which is present in complex predominantly with RGS9-2 rather than with RGS7. Changes in the neuronal excitability or oxygenation status resulting in extracellular calcium entry, uncouples RGS9-2 from R7BP, triggering its selective degradation. Concurrently, released R7BP binds to mainly intracellular RGS7 and recruits it to the plasma membrane and the postsynaptic density. These observations introduce activity-dependent remodeling of R7 RGS complexes as a new molecular plasticity mechanism in striatal neurons and suggest a general model for achieving rapid posttranslational subunit rearrangement in multisubunit complexes.

Publication types

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

MeSH terms

  • Animals
  • Cattle
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • GTP-Binding Protein beta Subunits / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Neostriatum / cytology
  • Neostriatum / metabolism*
  • Neostriatum / ultrastructure
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein Subunits / metabolism*
  • Protein Transport
  • RGS Proteins / metabolism*
  • Recombinant Proteins / metabolism
  • Signal Transduction*
  • Transfection


  • GTP-Binding Protein beta Subunits
  • Gnb5 protein, mouse
  • Protein Subunits
  • R7BP protein, mouse
  • RGS Proteins
  • Recombinant Proteins
  • regulator of g-protein signaling 9