Metabotropic glutamate receptors (mGluRs) constitute an important class of receptors and are widespread in the nervous system. However, their mechanism of action is still poorly understood. O'Connor et al. describe a series of experiments designed to elucidate the molecular mechanism of how group III mGluRs cause presynaptic inhibition of hippocampal excitatory transmission. They show that the intracellular tail of mGluR7 binds calmodulin in a Ca2+-dependent manner. The intracellular part of the protein can also bind G-protein βγ subunits, but only in the absence of calmodulin, which suggests that binding of calmodulin and βγ subunit is mutually exclusive. The authors present a model in which Ca2+-influx during depolarization of the presynaptic terminal not only triggers neurotransmitter release but also activates calmodulin, which in turn releases βγ subunits from mGluRs, and subsequently induces presynaptic inhibition.
O'Connor, V., El Far, O., Bofill-Cardona, E., Nanoff, C., Freissmuth, M., Karschin, A., Airas, J.M., Betz, H., and Boehm, S. (1999) Calmodulin dependence of presynaptic metabotropic glutamate receptor signaling. Science 286: 1180-1184. [Abstract] [Full Text]