| First Author | Vigot R | Year | 2006 |
| Journal | Neuron | Volume | 50 |
| Issue | 4 | Pages | 589-601 |
| PubMed ID | 16701209 | Mgi Jnum | J:113340 |
| Mgi Id | MGI:3665427 | Doi | 10.1016/j.neuron.2006.04.014 |
| Citation | Vigot R, et al. (2006) Differential compartmentalization and distinct functions of GABAB receptor variants. Neuron 50(4):589-601 |
| abstractText | 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. |
