Postnatal Induction And Localization Of R7bp, A Membrane-Anchoring Protein For Regulator Of G Protein Signaling 7 Family-G Beta 5 Complexes In Brain

Members of the regulator of G protein signaling 7 (RGS7) (R7) family and G beta 5 form obligate heterodimers that are expressed predominantly in the nervous system. R7-G beta 5 heterodimers are GTPase-activating proteins (GAPs) specific for Gi/o-class G alpha subunits, which mediate phototransduction in retina and the action of many modulatory G protein-coupled receptors (GPCRs) in brain. Here we have focused on the R7-family binding protein (R7BP), a recently identified palmitoylated protein that can bind R7-G beta 5 complexes and is hypothesized to control the intracellular localization and function of the resultant heterotrimeric complexes. We show that: 1) R7-G beta 5 complexes are obligate binding partners for R7 beta P in brain because they co-immunoprecipitate and exhibit similar expression patterns. Furthermore, R7BP and R7 protein accumulation in vivo requires G beta 5.2) Expression of R7BP in Neuro2A cells at levels approximating those in brain recruits endogenous RGS7-G beta 5 complexes to the plasma membrane. 3) R7BP immunoreactivity in brain concentrates in neuronal soma, dendrites, spines or unmyelinated axons, and is absent or low in glia, myelinated axons, or axon terminals. 4) RGS7-G beta 5-R7BP complexes in brain extracts associate inefficiently with detergent-resistant lipid raft fractions with or without G protein activation. 5) R7BP and G beta 5 protein levels are upregulated strikingly during the first 2-3 weeks of postnatal brain development. Accordingly, we suggest that R7-G beta 5-R7BP complexes in the mouse or rat could regulate signaling by modulatory Gi/o-coupled GPCRs in the developing and adult nervous systems. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.