Presynaptic regulation of neurotransmission in Drosophila by the g protein-coupled receptor methuselah.
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 approximately 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.
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D029721:Drosophila Proteins / Q000172:deficiency* / Q000235:genetics; D004331:Drosophila melanogaster / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D005089:Exocytosis / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D007476:Ionophores; D007814:Larva / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D009046:Motor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009420:Nervous System / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D013570:Synaptic Membranes / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics*
D029721:Drosophila Proteins; D007476:Ionophores; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C115381:mth protein, Drosophila; D019204:GTP-Binding Proteins; D002118:Calcium