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

Laviv, T. and Vertkin, I. and Berdichevsky, Y. and Fogel, H. and Riven, I. and Bettler, B. and Slesinger, P. A. and Slutsky, I.. (2011) Compartmentalization of the GABAB receptor signaling complex is required for presynaptic inhibition at hippocampal synapses. Journal of Neuroscience, 31 (35). pp. 12523-12532.

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Official URL: http://edoc.unibas.ch/dok/A6006430

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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 ?) complexes between GABA(B) receptors composed of GB(1a)/GB(2) subunits, G?(o)?(1)?(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 the receptor, Ca(V)2.2 and G??, but was dispensable for agonist-induced receptor activation and cAMP inhibition. Functionally, boutons lacking this complex-formation domain displayed impaired presynaptic inhibition of Ca(2+) transients and synaptic vesicle release. Thus, compartmentalization of the GABA(B1a) receptor, G??, and Ca(V)2.2 channel in a signaling complex is required for presynaptic inhibition at hippocampal synapses.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
UniBasel Contributors:Bettler, Bernhard
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Society for Neuroscience
ISSN:0270-6474
e-ISSN:1529-2401
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:27 Nov 2017 14:11
Deposited On:16 Aug 2013 07:33

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