Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants

Réjan Vigot, Samuel Barbieri, Hans Bräuner-Osborne, Rostislav Turecek, Ryuichi Shigemoto, Yan-Ping Zhang, Rafael Luján, Laura H. Jacobson, Barbara Biermann, Jean-Marc Fritschy, Claire-Marie Vacher, Matthias Müller (+7 others)
2006 Neuron  
GABA B receptors are the G protein-coupled receptors for the main inhibitory neurotransmitter in the brain, g-aminobutyric acid (GABA). Molecular diversity in the GABA B system arises from the GABA B1a and GABA B1b subunit isoforms that solely differ in their ectodomains by a pair of sushi repeats that is unique to GABA B1a . Using a combined genetic, physiological, and morphological approach, we now demonstrate that GABA B1 isoforms localize to distinct synaptic sites and convey separate
more » ... ons in vivo. At hippocampal CA3-to-CA1 synapses, GABA B1a assembles heteroreceptors inhibiting glutamate release, while predominantly GABA B1b mediates postsynaptic inhibition. Electron microscopy reveals a synaptic distribution of GABA B1 isoforms that agrees with the observed functional differences. Transfected CA3 neurons selectively express GABA B1a in distal axons, suggesting that the sushi repeats, a conserved protein interaction motif, specify heteroreceptor localization. The constitutive absence of GABA B1a but not GABA B1b results in impaired synaptic plasticity and hippocampusdependent memory, emphasizing molecular differences in synaptic GABA B functions.
doi:10.1016/j.neuron.2006.04.014 pmid:16701209 pmcid:PMC3531664 fatcat:n6qzhw4zbvbcrkbmct4mzx66q4