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Differential compartmentalization and distinct functions of GABAB receptor variants

Vigot, Réjan and Barbieri, Samuel and Bräuner-Osborne, Hans and Turecek, Rostislav and Shigemoto, Ryuichi and Zhang, Yan-Ping and Luján, Rafael and Jacobson, Laura H. and Biermann, Barbara and Fritschy, Jean-Marc and Vacher, Claire-Marie and Müller, Matthias and Sansig, Gilles and Guetg, Nicole and Cryan, John F. and Kaupmann, Klemens and Gassmann, Martin and Oertner, Thomas G. and Bettler, Bernhard. (2006) Differential compartmentalization and distinct functions of GABAB receptor variants. Neuron, Vol. 50, H. 4. pp. 589-601.

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Official URL: http://edoc.unibas.ch/dok/A5262229

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Abstract

GABAB receptors are the G protein-coupled receptors for the main inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA). Molecular diversity in the GABAB system arises from the GABAB1a and GABAB1b subunit isoforms that solely differ in their ectodomains by a pair of sushi repeats that is unique to GABAB1a. Using a combined genetic, physiological, and morphological approach, we now demonstrate that GABAB1 isoforms localize to distinct synaptic sites and convey separate functions in vivo. At hippocampal CA3-to-CA1 synapses, GABAB1a assembles heteroreceptors inhibiting glutamate release, while predominantly GABAB1b mediates postsynaptic inhibition. Electron microscopy reveals a synaptic distribution of GABAB1 isoforms that agrees with the observed functional differences. Transfected CA3 neurons selectively express GABAB1a in distal axons, suggesting that the sushi repeats, a conserved protein interaction motif, specify heteroreceptor localization. The constitutive absence of GABAB1a but not GABAB1b results in impaired synaptic plasticity and hippocampus-dependent memory, emphasizing molecular differences in synaptic GABAB functions.
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:Cell Press
ISSN:0896-6273
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:36

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