Ca2+ activity at GABAB receptors constitutively promotes metabotropic glutamate signaling in the absence of GABA

Tabata, Toshihide and Araishi, Kenji and Hashimoto, Kouichi and Hashimotodani, Yuki and van der Putten, Herman and Bettler, Bernhard and Kano, Masanobu. (2004) Ca2+ activity at GABAB receptors constitutively promotes metabotropic glutamate signaling in the absence of GABA. Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 48. pp. 16952-16957.

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Official URL: http://edoc.unibas.ch/dok/A5262241

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Type B gamma-aminobutyric acid receptor (GABABR) is a G protein-coupled receptor that regulates neurotransmitter release and neuronal excitability throughout the brain. In various neurons, GABABRs are concentrated at excitatory synapses. Although these receptors are assumed to respond to GABA spillover from neighboring inhibitory synapses, their function is not fully understood. Here we show a previously undescribed function of GABABR exerted independent of GABA. In cerebellar Purkinje cells, interaction of GABABR with extracellular Ca2+ (Ca(2+)o) leads to a constitutive increase in the glutamate sensitivity of metabotropic glutamate receptor 1 (mGluR1). mGluR1 sensitization is clearly mediated by GABABR because it is absent in GABABR1 subunit-knockout cells. However, the mGluR1 sensitization does not require G(i/o) proteins that mediate the GABABR's classical functions. Moreover, coimmunoprecipitation reveals complex formation between GABABR and mGluR1 in the cerebellum. These findings demonstrate that GABABR can act as Ca(2+)o-dependent cofactors to enhance neuronal metabotropic glutamate signaling.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
UniBasel Contributors:Bettler, Bernhard
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:34

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