期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 48, 页码 16952-16957出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0405387101
关键词
calcium; cerebellum; G protein-coupled receptor; oligomerization; Purkinje cell
Type B gamma-aminobutyric acid receptor (GABA(B)R) is a G protein-coupled receptor that regulates neurotransmitter release and neuronal excitability throughout the brain. In various neurons, GABA(B)Rs 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 GABA(B)R exerted independent of GABA. In cerebellar Purkinje cells, interaction of GABA(B)R with extracellular Ca2+ (Ca-o(2+)) 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 GABA(B)R1 subunit-knockout cells. However, the mGIuR1 sensitization does not require G(i/o) proteins that mediate the GABABR's classical functions. Moreover, coimmunoprecipitation reveals complex formation between GABA(B)R and nl in the cerebellum. These findings demonstrate that GABA(B)R can act as Ca-o(2+)-dependent cofactors to enhance neuronal metabotropic glutamate signaling.
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