Publication Date:
1999-11-05
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connor, V -- El Far, O -- Bofill-Cardona, E -- Nanoff, C -- Freissmuth, M -- Karschin, A -- Airas, J M -- Betz, H -- Boehm, S -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1180-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10550060" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Calcium/metabolism
;
Calmodulin/antagonists & inhibitors/*metabolism
;
Cells, Cultured
;
Dimerization
;
G Protein-Coupled Inwardly-Rectifying Potassium Channels
;
GTP-Binding Proteins/*metabolism
;
Glutamic Acid/*metabolism
;
Hippocampus/cytology/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/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Sesterterpenes
;
Signal Transduction
;
Swine
;
*Synaptic Transmission
;
Terpenes/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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