The V-ATPase V0 Subunit A1 is Required for a Late Step in Synaptic Vesicle Exocytosis in Drosophila

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2005 May 24

PMID 15907473

Citations 144

Authors

P Robin Hiesinger

Amir Fayyazuddin

Sunil Q Mehta

Tanja Rosenmund

Karen L Schulze

R Grace Zhai

Patrik Verstreken

Yu Cao

Yi Zhou

Jeannette Kunz

Hugo J Bellen

Affiliations

Soon will be listed here.

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.

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References

Peters C, Bayer M, Buhler S, Andersen J, Mann M, Mayer A . Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion. Nature. 2001; 409(6820):581-8. DOI: 10.1038/35054500. View

Perzov N, Padler-Karavani V, Nelson H, Nelson N . Characterization of yeast V-ATPase mutants lacking Vph1p or Stv1p and the effect on endocytosis. J Exp Biol. 2002; 205(Pt 9):1209-19. DOI: 10.1242/jeb.205.9.1209. View

Morel N . Neurotransmitter release: the dark side of the vacuolar-H+ATPase. Biol Cell. 2003; 95(7):453-7. DOI: 10.1016/s0248-4900(03)00075-3. View

Brand A, Perrimon N . Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993; 118(2):401-15. DOI: 10.1242/dev.118.2.401. View

Newsome T, Asling B, Dickson B . Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics. Development. 2000; 127(4):851-60. DOI: 10.1242/dev.127.4.851. View

Kuromi H, Kidokoro Y . Tetanic stimulation recruits vesicles from reserve pool via a cAMP-mediated process in Drosophila synapses. Neuron. 2000; 27(1):133-43. DOI: 10.1016/s0896-6273(00)00015-5. View

Drose S, Altendorf K . Bafilomycins and concanamycins as inhibitors of V-ATPases and P-ATPases. J Exp Biol. 1997; 200(Pt 1):1-8. DOI: 10.1242/jeb.200.1.1. View

Thorngren N, Collins K, Fratti R, Wickner W, Merz A . A soluble SNARE drives rapid docking, bypassing ATP and Sec17/18p for vacuole fusion. EMBO J. 2004; 23(14):2765-76. PMC: 514947. DOI: 10.1038/sj.emboj.7600286. View

Sorensen J . Formation, stabilisation and fusion of the readily releasable pool of secretory vesicles. Pflugers Arch. 2004; 448(4):347-62. DOI: 10.1007/s00424-004-1247-8. View

10.

Hu C, Ahmed M, Melia T, Sollner T, Mayer T, Rothman J . Fusion of cells by flipped SNAREs. Science. 2003; 300(5626):1745-9. DOI: 10.1126/science.1084909. View

11.

Hiesinger P, Reiter C, Schau H, Fischbach K . Neuropil pattern formation and regulation of cell adhesion molecules in Drosophila optic lobe development depend on synaptobrevin. J Neurosci. 1999; 19(17):7548-56. PMC: 6782525. View

12.

Nishi T, Forgac M . The vacuolar (H+)-ATPases--nature's most versatile proton pumps. Nat Rev Mol Cell Biol. 2002; 3(2):94-103. DOI: 10.1038/nrm729. View

13.

Nelson N . A journey from mammals to yeast with vacuolar H+-ATPase (V-ATPase). J Bioenerg Biomembr. 2003; 35(4):281-9. DOI: 10.1023/a:1025768529677. View

14.

Lindau M, Almers W . Structure and function of fusion pores in exocytosis and ectoplasmic membrane fusion. Curr Opin Cell Biol. 1995; 7(4):509-17. DOI: 10.1016/0955-0674(95)80007-7. View

15.

SCHULZE K, Broadie K, Perin M, Bellen H . Genetic and electrophysiological studies of Drosophila syntaxin-1A demonstrate its role in nonneuronal secretion and neurotransmission. Cell. 1995; 80(2):311-20. DOI: 10.1016/0092-8674(95)90414-x. View

16.

Bennett M, Calakos N, Kreiner T, Scheller R . Synaptic vesicle membrane proteins interact to form a multimeric complex. J Cell Biol. 1992; 116(3):761-75. PMC: 2289316. DOI: 10.1083/jcb.116.3.761. View

17.

Bayer M, Reese C, Buhler S, Peters C, Mayer A . Vacuole membrane fusion: V0 functions after trans-SNARE pairing and is coupled to the Ca2+-releasing channel. J Cell Biol. 2003; 162(2):211-22. PMC: 2172786. DOI: 10.1083/jcb.200212004. View

18.

Jena B . Discovery of the Porosome: revealing the molecular mechanism of secretion and membrane fusion in cells. J Cell Mol Med. 2004; 8(1):1-21. PMC: 6740243. DOI: 10.1111/j.1582-4934.2004.tb00255.x. View

19.

Aravamudan B, Fergestad T, Davis W, Rodesch C, Broadie K . Drosophila UNC-13 is essential for synaptic transmission. Nat Neurosci. 1999; 2(11):965-71. DOI: 10.1038/14764. View

20.

Miesenbock G, De Angelis D, Rothman J . Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature. 1998; 394(6689):192-5. DOI: 10.1038/28190. View