Editors' ChoiceNeurotransmission

Methuselah Increases the Docked Pool

Science's STKE  08 Oct 2002:
Vol. 2002, Issue 153, pp. tw367-TW367
DOI: 10.1126/stke.2002.153.tw367

Song et al. found a decrease in synaptic transmission at the Drosophila neuromuscular junctions in flies with a disrupted methuselah (mth) gene, which encodes a putative G protein-coupled receptor (GPCR). Loss of function of Mth extends fly life-span. The mutant flies had normal numbers and gross morphology of synaptic boutons, but decreased density of synaptic vesicles docked at active zones. Regulation of the availability and exocytosis of synaptic vesicles contributes to synaptic strength. Acute expression of mth in the nerve, but not the muscle, restored synaptic transmission to wild type and restored docked synaptic vesicle density. Overexpression of mth increased synaptic transmission (measured excitatory junctional potentials). Phorbol esters can stimulate a diacylglycerol pathway in wild-type flies resulting in enhanced synaptic transmission, but this stimulation was lost in the mth mutant flies. The ligand for this orphan GPCR and the downstream signaling pathway that regulates the availability of docked vesicles for neuromuscular transmission remain unknown. Whether there is a connection between role of Mth in synaptic transmission and its role in life-span also remains a mystery.

W. Song, R. Ranjan, K. Dawson-Scully, P. Bronk, L. Marin, L. Seroude, Y.-J. Lin, Z. Nie, H. L. Atwood, S. Benser, K. E. Zinsmaier, Presynaptic regulation of neurotransmission in Drosophila by the G protein-coupled receptor Methuselah. Neuron 36, 105-119 (2002). [Online Journal]