Ca2+ activity at GABAB receptors constitutively promotes metabotropic glutamate signaling in the absence of GABA
AUTOR(ES)
Tabata, Toshihide
FONTE
National Academy of Sciences
RESUMO
Type B γ-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+ (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{Ca}}_{{\mathrm{o}}}^{2+}\end{equation*}\end{document}) 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 Gi/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 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{Ca}}_{{\mathrm{o}}}^{2+}\end{equation*}\end{document}-dependent cofactors to enhance neuronal metabotropic glutamate signaling.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=529326Documentos Relacionados
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