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GABA-B1 Receptors are Coupled to the ERK1/2 MAP Kinase Pathway in the Absence of GABA-B2 Subunits

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Abstract

In the current model of γ-aminobutyric acid (GABA) B receptor function, there is a requirement for GABA-B1/2 heterodimerisation for targetting to the cell surface. However, different lines of evidence suggest that the GABA-B1 subunit can form a functional receptor in the absence of GABA-B2. We observed coupling of endogenous GABA-B1 receptors in the DI-TNC1 glial cell line to the ERK pathway in response to baclofen even though these cells do not express GABA-B2. GABA-B1A receptors were also able to mediate a rapid, transient, and dose-dependent activation of the ERK1/2 MAP kinase pathway when transfected alone into HEK 293 cells. The response was abolished by Gi/o and MEK inhibition, potentiated by inhibitors of phospholipase C and protein kinase C and did not involve PI-3-kinase activity. Finally, using bioluminescence resonance energy transfer and co-immunoprecipitation, we show the existence of homodimeric GABA-B1A receptors in transfected HEK293 cells. Altogether, our observations show that GABA-B1A receptors are able to activate the ERK1/2 pathway despite the absence of surface targetting partner GABA-B2 in both HEK 293 cells and the DI-TNC1 cell line.

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Acknowledgements

This work was supported by grant MOP-79354 from the Canadian Institutes of Health Research to T.E.H. T.E.H. is a Chercheur National of the Fonds de Recherche en Santé du Québec. M.R. was supported by a scholarship from the Canadian Institutes of Health Research. We would like to thank Bruce Allen and Jean-Philippe Pin for helpful discussions.

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Authors and Affiliations

  1. Département de biochimie and Groupe de recherche universitaire sur le médicament (GRUM), Université de Montréal, Montréal, Québec, Canada

    Maxime Richer, Martin David & Terence E. Hébert

  2. Centre de recherche, Institut de Cardiologie de Montréal, Montréal, Québec, Canada

    Louis R. Villeneuve & Aida M. Mamarbachi

  3. Department of Pharmacology and Therapeutics, McGill University, Room 1303 McIntyre Medical Sciences Building, 3655 Promenade Sir-William-Osler, Montréal, Québec, H3G 1Y6, Canada

    Phan Trieu, Nathalie Ethier, Darlaine Pétrin & Terence E. Hébert

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  1. Maxime Richer
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  2. Martin David
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  3. Louis R. Villeneuve
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Correspondence to Terence E. Hébert.

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Richer, M., David, M., Villeneuve, L.R. et al. GABA-B1 Receptors are Coupled to the ERK1/2 MAP Kinase Pathway in the Absence of GABA-B2 Subunits. J Mol Neurosci 38, 67–79 (2009). https://doi.org/10.1007/s12031-008-9163-6

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