title: The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila.
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.
authors.affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: P Robin
authors.initials: PR
authors.lastname: Hiesinger
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Amir
authors.initials: A
authors.lastname: Fayyazuddin
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Sunil Q
authors.initials: SQ
authors.lastname: Mehta
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Tanja
authors.initials: T
authors.lastname: Rosenmund
authors.affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Schulze
authors.affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: R Grace
authors.initials: RG
authors.lastname: Zhai
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Patrik
authors.initials: P
authors.lastname: Verstreken
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Kunz
authors.affiliation: 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.
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Bellen
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000378:metabolism* / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000648:ultrastructure; D005089:Exocytosis / Q000502:physiology*; D005124:Eye Abnormalities / Q000235:genetics; D006982:Hypertonic Solutions / Q000494:pharmacology; D008561:Membrane Fusion / Q000502:physiology*; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D017956:Photoreceptor Cells, Invertebrate / Q000002:abnormalities / Q000648:ultrastructure; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011726:Pyridinium Compounds / Q000493:pharmacokinetics; D000644:Quaternary Ammonium Compounds / Q000493:pharmacokinetics; D050600:SNARE Proteins; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: C073804:FM1 43; D006982:Hypertonic Solutions; D021122:Protein Subunits; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D025262:Vacuolar Proton-Translocating ATPases