Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants
2006
GABAB receptorsare 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
ectodomainsby 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
heteroreceptorsinhibiting 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
heteroreceptorlocalization. The constitutive absence of GABAB1a but not GABAB1b results in impaired
synaptic plasticityand hippocampus-dependent memory, emphasizing molecular differences in synaptic GABAB functions.
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