Drosophila metabotropic glutamate receptors: Structure and functions

M.L. Parmentier, A. Ramaekers & J. Bockaert

CNRS, UPR9023: Mecanismes Moleculaires des Communications Cellulaires, 141, rue de la Cardonille, 34094 Montpellier Cedex05, France

In Drosophila, glutamate is the excitatory neurotransmitter at the neuromuscular junction. Although it is also recognized as being a neurotransmitter in the central nervous system (CNS) of arthropods, little is known about its function. Glutamate is also the major excitatory neurotransmitter of the mammalian CNS. Its actions are mediated by glutamate-gated channels, and G protein-coupled receptors known as metabotropic receptors. Metabotropic receptors are thought to play key roles in important neuronal processes, ranging from developmental plasticity to memory. We cloned a Drosophila metabotropic glutamate receptor, that we called DmGluRA. This receptor shows a high affinity for glutamate and a remarkable conservation of the pharmacological profile and the transduction mechanism with that of group II mammalian mGluRs. We have constructed chimeric receptors between DmGluRA and the most distant mammalian mGluR and have shown that the extracellular domain and the seven transmembrane domain are interchangeable, the former being responsible for the ligand recognition, the latter for the G-protein activation. DmGluRA is expressed in the brain and the ventral nervous system, from embryo to the adult An antibody raised against a peptide based on the C-terminal derived amino acid sequence from DmGluRA was used to investigate localization of the receptor in the larvae and adult. Strong staining is detected in the antennal lobe glomeruli, and in the fan-shaped body of the central complex. Also stained are the medulla of the optic lobes. These results suggest possible roles for DmGluRA in the processing of olfactory, visual and locomotor information in the central nervous system of Drosophila melanogaster.

Index terms: G Protein-coupled receptors, pharmacology, central nervous system

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