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Cell. 2005 May 20;121(4):607-620. doi: 10.1016/j.cell.2005.03.012.

The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila.

Author information

1
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
2
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.
3
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030.
4
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
5
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030; Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030; Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030. Electronic address: hbellen@bcm.tmc.edu.

Abstract

The V(0) 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 V(0) 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.

Comment in

PMID:
15907473
PMCID:
PMC3351201
DOI:
10.1016/j.cell.2005.03.012
[Indexed for MEDLINE]
Free PMC Article

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