Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants

R. Vigot, S. Barbieri, H. Bräuner Osborne, R. Tureček, R. Shigemoto, Y. Zhang, R. Luján, L. Jacobson, B. Biermann, J. Fritschy, C. Vacher, M. Müller, G. Sansig, N. Guetg, J. Cryan, K. Kaupmann, M. Gassmann, T. Oertner, B. Bettler, Neuron 50 (2006) 589–601.

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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.
Publishing Year
Date Published
2006-05-18
Journal Title
Neuron
Volume
50
Issue
4
Page
589 - 601
IST-REx-ID

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Vigot R, Barbieri S, Bräuner Osborne H, et al. Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants. Neuron. 2006;50(4):589-601. doi:10.1016/j.neuron.2006.04.014
Vigot, R., Barbieri, S., Bräuner Osborne, H., Tureček, R., Shigemoto, R., Zhang, Y., … Bettler, B. (2006). Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants. Neuron, 50(4), 589–601. https://doi.org/10.1016/j.neuron.2006.04.014
Vigot, Réjan, Samuel Barbieri, Hans Bräuner Osborne, Rostislav Tureček, Ryuichi Shigemoto, Yan Zhang, Rafael Luján, et al. “Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants.” Neuron 50, no. 4 (2006): 589–601. https://doi.org/10.1016/j.neuron.2006.04.014.
R. Vigot et al., “Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants,” Neuron, vol. 50, no. 4, pp. 589–601, 2006.
Vigot R, Barbieri S, Bräuner Osborne H, Tureček R, Shigemoto R, Zhang Y, Luján R, Jacobson L, Biermann B, Fritschy J, Vacher C, Müller M, Sansig G, Guetg N, Cryan J, Kaupmann K, Gassmann M, Oertner T, Bettler B. 2006. Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants. Neuron. 50(4), 589–601.
Vigot, Réjan, et al. “Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants.” Neuron, vol. 50, no. 4, Elsevier, 2006, pp. 589–601, doi:10.1016/j.neuron.2006.04.014.

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