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.
O'Connor
V
V
Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.
El Far
O
O
Bofill-Cardona
E
E
Nanoff
C
C
Freissmuth
M
M
Karschin
A
A
Airas
J M
JM
Betz
H
H
Boehm
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D019281:Dimerization; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D017729:Presynaptic Terminals / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D054830:Sesterterpenes; D015398:Signal Transduction; D013552:Swine; D009435:Synaptic Transmission; D013729:Terpenes / Q000494:pharmacology
C114785:2-amino-4-phosphono-propinate; D002147:Calmodulin; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; D011993:Recombinant Fusion Proteins; D054830:Sesterterpenes; D013729:Terpenes; C102719:metabotropic glutamate receptor 7; D018698:Glutamic Acid; C040764:ophiobolin A; D019204:GTP-Binding Proteins; D002118:Calcium