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

Toshihide Tabata, Kenji Araishi, Kouichi Hashimoto, Yuki Hashimotodani, Herman Van Der Putten, Bernhard Bettler, Masanobu Kano*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

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+ (Ca o2+) 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 BR1 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 Cao2+- dependent cofactors to enhance neuronal metabotropic glutamate signaling.

Original languageEnglish
Pages (from-to)16952-16957
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number48
DOIs
StatePublished - 2004/11/30

Keywords

  • Calcium
  • Cerebellum
  • G protein-coupled receptor
  • Oligomerization
  • Purkinje cell

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Ca2+ activity at GABAB receptors constitutively promotes metabotropic glutamate signaling in the absence of GABA'. Together they form a unique fingerprint.

Cite this