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Science 286 (5442): 1180-1184

Copyright © 1999 by the American Association for the Advancement of Science

Calmodulin Dependence of Presynaptic Metabotropic Glutamate Receptor Signaling

Vincent O'Connor, 1*dagger Oussama El Far, 1* Elisa Bofill-Cardona, 2 Christian Nanoff, 2 Michael Freissmuth, 2 Andreas Karschin, 3 José M. Airas, 1 Heinrich Betz, 1ddagger Stefan Boehm 2

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) beta gamma 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 Ca2+-calmodulin is required to release G protein beta gamma subunits from the C-tail of group III mGluRs in order to mediate glutamatergic autoinhibition.

1 Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.
2 Institute of Pharmacology, University of Vienna, Währingerstrasse 13a, 1090 Vienna, Austria.
3 Molecular Neurobiology of Signal Transduction, Max Planck Institute for Biophysical Chemistry, 37070 Göttingen, Germany.
*   These authors contributed equally to this report.

dagger    Present address: University of Southampton, Biomedical Sciences Building, Basset Crescent East, Southampton SO16 7PX, UK.

ddagger    To whom correspondence should be addressed. E-mail: neurochemie{at}mpih-frankfurt.mpg.de


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