Calmodulin dependence of presynaptic metabotropic glutamate receptor signaling.
Glutamatergic neurotransmission is controlled by presynaptic metabotropic glutamate receptors (mGluRs). A subdomain in the intracellular carboxyl-terminal tail of group III mGluRs binds calmodulin and heterotrimeric guanosine triphosphate-binding protein (G protein) betagamma subunits in a mutually exclusive manner. Mutations interfering with calmodulin binding and calmodulin antagonists inhibit G protein-mediated modulation of ... ionic currents by mGluR 7. Calmodulin antagonists also prevent inhibition of excitatory neurotransmission via presynaptic mGluRs. These results reveal a novel mechanism of presynaptic modulation in which Ca(2+)-calmodulin is required to release G protein betagamma subunits from the C-tail of group III mGluRs in order to mediate glutamatergic autoinhibition.
Mesh Terms:
Amino Acid Sequence, Animals, Calcium, Calmodulin, Cells, Cultured, Dimerization, G Protein-Coupled Inwardly-Rectifying Potassium Channels, GTP-Binding Proteins, Glutamic Acid, Hippocampus, Humans, Mice, Molecular Sequence Data, Neurons, Potassium Channels, Potassium Channels, Inwardly Rectifying, Presynaptic Terminals, Propionic Acids, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate, Recombinant Fusion Proteins, Sesterterpenes, Signal Transduction, Swine, Synaptic Transmission, Terpenes
Amino Acid Sequence, Animals, Calcium, Calmodulin, Cells, Cultured, Dimerization, G Protein-Coupled Inwardly-Rectifying Potassium Channels, GTP-Binding Proteins, Glutamic Acid, Hippocampus, Humans, Mice, Molecular Sequence Data, Neurons, Potassium Channels, Potassium Channels, Inwardly Rectifying, Presynaptic Terminals, Propionic Acids, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate, Recombinant Fusion Proteins, Sesterterpenes, Signal Transduction, Swine, Synaptic Transmission, Terpenes
Science
Date: Nov. 05, 1999
PubMed ID: 10550060
View in: Pubmed Google Scholar
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