Differential compartmentalization and distinct functions of GABAB receptor variants.
Differential compartmentalization and distinct functions of GABAB receptor variants.
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DOI：
10.1016/j.neuron.2006.04.014
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发表时间：
2006-05-18
期刊：
影响因子：
16.2
通讯作者：
Bettler B
中科院分区：
文献类型：
--
作者：
Vigot R;Barbieri S;Bräuner-Osborne H;Turecek R;Shigemoto R;Zhang YP;Luján R;Jacobson LH;Biermann B;Fritschy JM;Vacher CM;Müller M;Sansig G;Guetg N;Cryan JF;Kaupmann K;Gassmann M;Oertner TG;Bettler B
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.
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