Calmodulin Dependence of Presynaptic Metabotropic Glutamate Receptor Signaling

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Science  05 Nov 1999:
Vol. 286, Issue 5442, pp. 1180-1184
DOI: 10.1126/science.286.5442.1180

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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) βγ 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 βγ subunits from the C-tail of group III mGluRs in order to mediate glutamatergic autoinhibition.

  • * These authors contributed equally to this report.

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

  • To whom correspondence should be addressed. E-mail: neurochemie{at}

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