Dominant role of GABAB2 and Gbetagamma for GABAB receptor-mediated-ERK1/2/CREB pathway in cerebellar neurons

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dc.creatorTu, Haijun
dc.creatorRondard, Philippe
dc.creatorXu, Chanjuan
dc.creatorBertaso, Federica
dc.creatorCao, Fangli
dc.creatorZhang, Xueying
dc.creatorPin, Jean-Philippe
dc.creatorLiu, Jianfeng
dc.date2008-09-10
dc.date.accessioned2026-07-07T10:01:58Z
dc.date.available2026-07-07T10:01:58Z
dc.descriptiongamma-aminobutyric acid type B (GABA(B)) receptor is an allosteric complex made of two subunits, GABA(B1) and GABA(B2). GABA(B2) plays a major role in the coupling to G protein whereas GABA(B1) binds GABA. It has been shown that GABA(B) receptor activates ERK(1/2) in neurons of the central nervous system, but the molecular mechanisms underlying this event are poorly characterized. Here, we demonstrate that activation of GABA(B) receptor by either GABA or the selective agonist baclofen induces ERK(1/2) phosphorylation in cultured cerebellar granule neurons. We also show that CGP7930, a positive allosteric regulator specific of GABA(B2), alone can induce the phosphorylation of ERK(1/2). PTX, a G(i/o) inhibitor, abolishes both baclofen and CGP7930-mediated-ERK(1/2) phosphorylation. Moreover, both baclofen and CGP7930 induce ERK-dependent CREB phosphorylation. Furthermore, by using LY294002, a PI-3 kinase inhibitor, and a C-term of GRK-2 that has been reported to sequester Gbetagamma subunits, we demonstrate the role of Gbetagamma in GABA(B) receptor-mediated-ERK(1/2) phosphorylation. In conclusion, the activation of GABA(B) receptor leads to ERK(1/2) phosphorylation via the coupling of GABA(B2) to G(i/o) and by releasing Gbetagamma subunits which in turn induce the activation of CREB. These findings suggest a role of GABA(B) receptor in long-term change in the central nervous system.
dc.identifierhttps://arxiv.org/abs/0809.1718
dc.identifierhttp://arxiv.org/abs/0809.1718
dc.identifierCellular Signalling 19, 9 (2007) 1996-2002
dc.identifierdoi:10.1016/j.cellsig.2007.05.004
dc.identifier.urihttp://salesiana.dossiersoluciones.com/handle/123456789/168813
dc.subjectNeurons and Cognition
dc.titleDominant role of GABAB2 and Gbetagamma for GABAB receptor-mediated-ERK1/2/CREB pathway in cerebellar neurons
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