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G Protein-Coupled Glutamate and GABA Receptors Form Complexes and Mutually Modulate Their Signals
journal contribution
posted on 2020-02-05, 15:08 authored by Hakushun Sakairi, Yuji Kamikubo, Masayoshi Abe, Keisuke Ikeda, Arata Ichiki, Toshihide Tabata, Masanobu Kano, Takashi SakuraiMolecular
networks containing various proteins mediate many types
of cellular processes. Elucidation of how the proteins interact will
improve our understanding of the molecular integration and physiological
and pharmacological propensities of the network. One of the most complicated
and unexplained interactions between proteins is the inter-G protein-coupled
receptor (GPCR) interaction. Recently, many studies have suggested
that an interaction between neurotransmitter GPCRs may mediate diverse
modalities of neural responses. The B-type gamma-aminobutyric acid
(GABA) receptor (GBR) and type-1 metabotropic glutamate receptor (mGluR1)
are GPCRs for GABA and glutamate, respectively, and each plays distinct
roles in controlling neurotransmission. We have previously reported
the possibility of their functional interaction in central neurons.
Here, we examined the interaction of these GPCRs using stable cell
lines and rat cerebella. Cell-surface imaging and coimmunoprecipitation
analysis revealed that these GPCRs interact on the cell surface. Furthermore,
fluorometry revealed that these GPCRs mutually modulate signal transduction.
These findings provide solid evidence that mGluR1 and GBR have intrinsic
abilities to form complexes and to mutually modulate signaling. These
findings indicate that synaptic plasticity relies on a network of
proteins far more complex than previously assumed.
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Cell-surface imagingform complexessynaptic plasticitycell surfacemetabotropic glutamate receptorinter-G protein-coupled receptorcoimmunoprecipitation analysismGluR 1G Protein-Coupled GlutamateGABA Receptors Form Complexesneurotransmitter GPCRsrat cerebellainteractionSignals Molecular networkssignal transductionMutually ModulateB-type gamma-aminobutyric acidGBRcell lines
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