Compartmentalization of the GABAB receptor signaling complex is required for presynaptic inhibition at hippocampal synapses.

ABSTRACT: Presynaptic inhibition via G-protein-coupled receptors (GPCRs) and voltage-gated Ca(2+) channels constitutes a widespread regulatory mechanism of synaptic strength. Yet, the mechanism of intermolecular coupling underlying GPCR-mediated signaling at central synapses remains unresolved. Using FRET spectroscopy, we provide evidence for formation of spatially restricted (<100 Å) complexes between GABA(B) receptors composed of GB(1a)/GB(2) subunits, Gα(o)β(1)γ(2) G-protein heterotrimer, and Ca(V)2.2 channels in hippocampal boutons. GABA release was not required for the assembly but for structural reorganization of the precoupled complex. Unexpectedly, GB(1a) deletion disrupted intermolecular associations within the complex. The GB(1a) proximal C-terminal domain was essential for association of

SUBMITTER: Laviv T 

PROVIDER: S-EPMC6703276 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature