Presynaptic regulation of neurotransmission in Drosophila by the G protein-coupled receptor Methuselah

Wei Song, Ravi Ranjan, Ken Dawson-Scully, Peter Bronk, Leo Marin, Laurent Seroude, Yi-Jyun Lin, Zhiping Nie, Harold L. Atwood, Seymour Benzer, and Konrad E. Zinsmaier

Department of Neuroscience University of Pennsylvania School of Medicine Philadelphia, Pennsylvania 19104
Division of Biology California Institute of Technology 156-29 Pasadena, California 91125
Department of Physiology University of Toronto Toronto, Ontario M5S 1A8 Canada
Division of Neurobiology Arizona Research Laboratories University of Arizona Tucson, Arizona 85721

Regulation of synaptic strength is essential for neuronal information processing, but the molecular mechanisms that control changes in neuroexocytosis are only partially known. Here we show that the putative G protein-coupled receptor Methuselah (Mth) is required in the presynaptic motor neuron to acutely upregulate neurotransmitter exocytosis at larval Drosophila NMJs. Mutations in the mth gene reduce evoked neurotransmitter release by ~50%, and decrease synaptic area and the density of docked and clustered vesicles. Pre but not postsynaptic expression of normal Mth restored normal release in mth mutants. Conditional expression of Mth restored normal release and normal vesicle docking and clustering but not the reduced size of synaptic sites, suggesting that Mth acutely adjusts vesicle trafficking to synaptic sites.