Calmodulin dependence of presynaptic metabotropic glutamate receptor signaling

V O'Connor; O El Far; E Bofill-Cardona; C Nanoff; M Freissmuth; A Karschin; J M Airas; H Betz; S Boehm

doi:10.1126/science.286.5442.1180

Calmodulin dependence of presynaptic metabotropic glutamate receptor signaling

Science. 1999 Nov 5;286(5442):1180-4. doi: 10.1126/science.286.5442.1180.

Authors

V O'Connor¹, O El Far, E Bofill-Cardona, C Nanoff, M Freissmuth, A Karschin, J M Airas, H Betz, S Boehm

Affiliation

¹ Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.

PMID: 10550060
DOI: 10.1126/science.286.5442.1180

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Calcium / metabolism
Calmodulin / antagonists & inhibitors
Calmodulin / metabolism*
Cells, Cultured
Dimerization
G Protein-Coupled Inwardly-Rectifying Potassium Channels
GTP-Binding Proteins / metabolism*
Glutamic Acid / metabolism*
Hippocampus / cytology
Hippocampus / metabolism
Humans
Mice
Molecular Sequence Data
Neurons / metabolism
Potassium Channels / metabolism
Potassium Channels, Inwardly Rectifying*
Presynaptic Terminals / metabolism
Propionates / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate / antagonists & inhibitors
Receptors, Metabotropic Glutamate / metabolism*
Recombinant Fusion Proteins / metabolism
Sesterterpenes
Signal Transduction
Swine
Synaptic Transmission*
Terpenes / pharmacology

Substances

2-amino-4-phosphono-propinate
Calmodulin
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Potassium Channels
Potassium Channels, Inwardly Rectifying
Propionates
Receptors, Metabotropic Glutamate
Recombinant Fusion Proteins
Sesterterpenes
Terpenes
metabotropic glutamate receptor 7
Glutamic Acid
ophiobolin A
GTP-Binding Proteins
Calcium