Membrane anchoring subunits specify selective regulation of RGS9·Gbeta5 GAP complex in photoreceptor neurons

J Neurosci. 2010 Oct 13;30(41):13784-93. doi: 10.1523/JNEUROSCI.1191-10.2010.


The RGS9·Gβ5 complex is the key regulator of neuronal G-protein signaling and shows remarkable selectivity of subunit composition. In retinal photoreceptors, RGS9·Gβ5 is bound to the membrane anchor R9AP and the complex regulates visual signaling. In the basal ganglia neurons, RGS9·Gβ5 is instead associated with a homologous protein, R7BP, and regulates reward circuit. Switching this selective subunit composition of the complex in rod photoreceptors allowed us to study the molecular underpinning of signaling specificity in diverse G-protein pathways. We have found that both membrane anchoring subunits play a conserved role in regulating protein levels of RGS9·Gβ5 and enhancing the ability of RGS·Gβ5 complexes to stimulate GTPase activity of G proteins. However, notable differences exist in the subcellular targeting of alternatively configured complexes. Unlike R9AP, which relies on passive targeting mechanisms for the delivery to the outer segments of the photoreceptors, R7BP is excluded from this location and is instead specifically targeted to the plasma membrane. R7BP-containing complexes could be rerouted to the outer segments, where they are capable of regulating the phototransduction cascade by the active targeting signals derived from rhodopsin. These findings illustrate the diversity of the G-protein signaling regulation by RGS·Gβ5 complexes achieved by differential recruitment of the membrane anchors.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Membrane / genetics
  • Cell Membrane / metabolism*
  • Electrophysiology
  • GTP-Binding Protein beta Subunits / genetics
  • GTP-Binding Protein beta Subunits / metabolism*
  • Immunohistochemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Photic Stimulation
  • Protein Binding
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Signal Transduction


  • GTP-Binding Protein beta Subunits
  • Gnb5 protein, mouse
  • Membrane Proteins
  • R9AP protein, mouse