@article{ef7e01c4c65446bf8b245bb6007f9d7e,
title = "The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila",
abstract = "The V0 complex forms the proteolipid pore of an ATPase that acidifies vesicles. In addition, an independent function in membrane fusion has been proposed largely based on yeast vacuolar fusion experiments. We have isolated mutations in the largest V0 component vha100-1 in flies in an unbiased genetic screen for synaptic malfunction. The protein is only required in neurons, colocalizes with markers for synaptic vesicles as well as active zones, and interacts with t-SNAREs. Loss of vha100-1 leads to vesicle accumulation in synaptic terminals, suggesting a deficit in release. The amplitude of spontaneous release events and release with hypertonic stimulation indicate normal levels of neurotransmitter loading, yet mutant embryos display severe defects in evoked synaptic transmission and FM1-43 uptake. Our data suggest that Vha100-1 functions downstream of SNAREs in synaptic vesicle fusion.",
author = "Hiesinger, {P. Robin} and Amir Fayyazuddin and Mehta, {Sunil Q.} and Tanja Rosenmund and Schulze, {Karen L.} and Zhai, {R. Grace} and Patrik Verstreken and Yu Cao and Yi Zhou and Jeannette Kunz and Bellen, {Hugo J.}",
note = "Funding Information: We would like to thank Alois Hofbauer, Sean Carroll, Morris Manolson, Larry Zipursky, Peter Bryant, and the Bloomington Stock Center and the University of Iowa Developmental Studies Hybridoma Bank for reagents. We especially thank Iris Salecker for providing the ey3.5 FLP flies prior to publication. We are indebted to Tim Fergestad and Kendal Broadie for helping with embryonic FM uptake protocols as well as Tom Lloyd for help with the Syntaxin suppressor screen. Scanning EM was performed at the High Resolution Microscopy Facility of the University of Texas MD Anderson Cancer Center with the help of Kenneth Dunner, Jr. We thank Christian Rosenmund and Erwin Neher for discussions and critical reading of the manuscript. P.R.H., A.F., R.G.Z., K.L.S., and H.J.B. are supported by the HHMI. P.R.H. was further supported by an EMBO long-term fellowship. This work was also supported by grants GM068098 from the National Institutes of Health and Q-1536 from the Welch Foundation (both to J.K.). H.J.B. is an HHMI Investigator. ",
year = "2005",
month = may,
day = "20",
doi = "10.1016/j.cell.2005.03.012",
language = "English (US)",
volume = "121",
pages = "607--620",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}