ENEURO.0193-21.2021.full.pdf (3.56 MB)
A novel neuron-specific regulator of the V-ATPase in Drosophila
journal contribution
posted on 2023-06-10, 02:03 authored by Amina Dulac, Sabi Abdul-Raouf Issa, Jun Sun, Giorgio Matassi, Célia Jonas, Baya Chérif-Zahar, Daniel Cattaert, Serge BirmanThe V-ATPase is a highly conserved enzymatic complex that ensures appropriate levels of organelle acidification in virtually all eukaryotic cells. While the general mechanisms of this proton pump have been well studied, little is known about the specific regulations of neuronal V-ATPase. Here, we studied CG31030, a previously uncharacterized Drosophila protein predicted from its sequence homology to be part of the V-ATPase family. In contrast to its ortholog ATP6AP1/VhaAC45 which is ubiquitous, we observed that CG31030 expression is apparently restricted to all neurons, and using CRISPR/Cas9-mediated gene tagging, that it is mainly addressed to synaptic terminals. In addition, we observed that CG31030 is essential for fly survival and that this protein co-immunoprecipitates with identified V-ATPase subunits, and in particular ATP6AP2. Using a genetically-encoded pH probe (VMAT-pHluorin) and electrophysiological recordings at the larval neuromuscular junction, we show that CG31030 knock-down induces a major defect in synaptic vesicle acidification and a decrease in quantal size, which is the amplitude of the postsynaptic response to the release of a single synaptic vesicle. These defects were associated with severe locomotor impairments. Overall, our data indicate that CG31030, which we renamed VhaAC45-related protein (VhaAC45RP), is a specific regulator of neuronal V-ATPase in Drosophila that is required for proper synaptic vesicle acidification and neurotransmitter release.
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Publication status
- Published
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- Published version
Journal
eNeuroISSN
2373-2822Publisher
Society for NeuroscienceExternal DOI
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5Volume
8Page range
1-22Event location
United StatesDepartment affiliated with
- Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-12-20First Open Access (FOA) Date
2021-12-20First Compliant Deposit (FCD) Date
2021-12-20Usage metrics
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