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

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

Research output: Contribution to journalArticle

214 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)607-620
Number of pages14
JournalCell
Volume121
Issue number4
DOIs
Publication statusPublished - May 20 2005
Externally publishedYes

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SNARE Proteins
Synaptic Vesicles
Exocytosis
Drosophila
Adenosine Triphosphatases
Fusion reactions
Proteolipids
Membrane Fusion
Presynaptic Terminals
Synaptic Transmission
Diptera
Neurotransmitter Agents
Embryonic Structures
Yeasts
Neurons
Yeast
Mutation
Membranes
Defects
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Hiesinger, P. R., Fayyazuddin, A., Mehta, S. Q., Rosenmund, T., Schulze, K. L., Zhai, R. G., ... Bellen, H. J. (2005). The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila. Cell, 121(4), 607-620. https://doi.org/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. / Hiesinger, P. Robin; Fayyazuddin, Amir; Mehta, Sunil Q.; Rosenmund, Tanja; Schulze, Karen L.; Zhai, R. Grace; Verstreken, Patrik; Cao, Yu; Zhou, Yi; Kunz, Jeannette; Bellen, Hugo J.

In: Cell, Vol. 121, No. 4, 20.05.2005, p. 607-620.

Research output: Contribution to journalArticle

Hiesinger, PR, Fayyazuddin, A, Mehta, SQ, Rosenmund, T, Schulze, KL, Zhai, RG, Verstreken, P, Cao, Y, Zhou, Y, Kunz, J & Bellen, HJ 2005, 'The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila', Cell, vol. 121, no. 4, pp. 607-620. https://doi.org/10.1016/j.cell.2005.03.012
Hiesinger PR, Fayyazuddin A, Mehta SQ, Rosenmund T, Schulze KL, Zhai RG et al. The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila. Cell. 2005 May 20;121(4):607-620. https://doi.org/10.1016/j.cell.2005.03.012
Hiesinger, P. Robin ; Fayyazuddin, Amir ; Mehta, Sunil Q. ; Rosenmund, Tanja ; Schulze, Karen L. ; Zhai, R. Grace ; Verstreken, Patrik ; Cao, Yu ; Zhou, Yi ; Kunz, Jeannette ; Bellen, Hugo J. / The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila. In: Cell. 2005 ; Vol. 121, No. 4. pp. 607-620.
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