Disease relevance of Glu-RA

• Drosophila melanogaster metabotropic glutamate receptor (DmGluRA) expressed by this novel strategy was purified to homogeneity, giving at least 3-fold higher yields than conventional baculovirus expression systems due to the higher membrane content of the PRCs [1].

High impact information on Glu-RA

• Herein, we demonstrate that treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium can rescue courtship and mushroom body defects observed in these flies [2].
• Glutamate-binding affinity of Drosophila metabotropic glutamate receptor is modulated by association with lipid rafts [3].
• We have shown that ligand binding to reconstituted DmGluRA requires the presence of ergosterol in the liposomes [Eroglu, C., Cronet, P., Panneels, V., Beaufils, P. & Sinning, I. (2002) EMBO Rep. 3, 491-496] [3].
• Our data suggest that sterol-rich lipid rafts act as positive allosteric regulators of DmGluRA [3].
• We therefore expressed an invertebrate biogenic amine receptor, the Drosophila octopamine receptor, in rat cortical neurons and compared octopamine receptor-mediated responses with those mediated by the group I metabotropic glutamate receptor, the endogenous Gq-coupled receptor in rat cortical neurons [4].

Biological context of Glu-RA

• These phenotypes are reminiscent of hyperexcitable mutants, suggesting a role of DmGluRA signaling in the regulation of presynaptic excitability properties [5].
• In contrast, the Drosophila genome encodes a single functional mGluR (DmGluRA), an ortholog of vertebrate group II mGluRs, greatly expediting the functional characterization of mGluR-mediated signaling in the nervous system [5].
• Null DmGluRA mutants are completely viable, and all of the basal NMJ synaptic transmission properties are normal [5].
• We show here that DmGluRA is expressed at the glutamatergic neuromuscular junction (NMJ), localized in periactive zones of presynaptic boutons but excluded from active sites [5].

Anatomical context of Glu-RA

• DmGluRA immunoreactivity was not detected at the larval neuromuscular junction nor in the body wall muscles [6].
• In particular, DmGluRA can be found in the antennal lobes, the optic lobes, the central complex, and the median bundle in the adult CNS [6].
• Distribution of metabotropic glutamate receptor DmGlu-A in Drosophila melanogaster central nervous system [6].
• DmGluRA, a Drosophila metabotropic glutamate receptor, activates G-protein inwardly rectifying potassium channels in Xenopus oocytes [7].
• These morphological changes bidirectionally correlate with DmGluRA levels in the presynaptic terminal [5].

Other interactions of Glu-RA

• The roles of glutamatergic synapses in the Drosophila melanogaster CNS were investigated, with focus on the study of DmGluRA, a G-protein-coupled glutamate receptor [6].
• Xenopus oocytes were coinjected with cDNAs encoding the Drosophila melanogaster metabotropic glutamate receptor (DmGluRA) and two mammalian G-protein inwardly rectifying potassium channel subunits (GIRK1 and GIRK2) [7].

References