Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants Journal Article

Author(s): Vigot, Réjan; Barbieri, Samuel; Bräuner-Osborne, Hans; Tureček, Rostislav; Shigemoto, Ryuichi; Zhang, Yan Ping; Luján, Rafael; Jacobson, Laura H; Biermann, Barbara; Fritschy, Jean-Marc; Vacher, Claire-Marie; Müller, Matthias P; Sansig, Gilles; Guetg, Nicole; Cryan, John F; Kaupmann, Klemens; Gassmann, Martin; Oertner, Thomas G; Bettler, Bernhard
Article Title: Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants
Abstract: GABAB receptors are the G protein-coupled receptors for the main inhibitory neurotransmitter in the brain, γ-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.
Journal Title: Neuron
Volume: 50
Issue 4
ISSN: 0896-6273
Publisher: Elsevier  
Date Published: 2006-05-18
Start Page: 589
End Page: 601
DOI: 10.1016/j.neuron.2006.04.014
Open access: no