Rabconnectin3α promotes stable activity of the H + pump on synaptic vesicles in hair cells

Zev Einhorn, Josef G. Trapani, Qianyong Liu, Teresa Nicolson

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Acidification of synaptic vesicles relies on the vacuolar-type ATPase (V-ATPase) and provides the electrochemical driving force for neurotransmitter exchange. The regulatory mechanisms that ensure assembly of the V-ATPase holoenzyme on synaptic vesicles are unknown. Rabconnectin3α (Rbc3α) is a potential candidate for regulation of V-ATPase activity because of its association with synaptic vesicles and its requirement for acidification of intracellular compartments. Here, we provide the first evidence for a role of Rbc3α in synaptic vesicle acidification and neurotransmission. In this study, we characterized mutant alleles of rbc3α isolated from a large-scale screen for zebrafish with auditory/vestibular defects. We show that Rbc3α is localized to basal regions of hair cells in which synaptic vesicles are present. To determine whether Rbc3α regulates V-ATPase activity, we examined the acidification of synaptic vesicles and localization of the V-ATPase in hair cells. In contrast to wild-type hair cells, we observed that synaptic vesicles had elevated pH, and a cytosolic subunit of the V-ATPase was no longer enriched in synaptic regions of mutant hair cells. As a consequence of defective acidification of synaptic vesicles, afferent neurons in rbc3α mutants had reduced firing rates and reduced accuracy of phase-locked action potentials in response to mechanical stimulation of hair cells. Collectively, our data suggest that Rbc3α modulates synaptic transmission in hair cells by promoting V-ATPase activity in synaptic vesicles.

Original languageEnglish (US)
Pages (from-to)11144-11156
Number of pages13
JournalJournal of Neuroscience
Volume32
Issue number32
DOIs
StatePublished - Aug 8 2012

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Proton Pumps
Synaptic Vesicles
Vacuolar Proton-Translocating ATPases
Synaptic Transmission
Afferent Neurons
Holoenzymes
Zebrafish
Action Potentials
Neurotransmitter Agents
Alleles

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Rabconnectin3α promotes stable activity of the H + pump on synaptic vesicles in hair cells. / Einhorn, Zev; Trapani, Josef G.; Liu, Qianyong; Nicolson, Teresa.

In: Journal of Neuroscience, Vol. 32, No. 32, 08.08.2012, p. 11144-11156.

Research output: Contribution to journalArticle

Einhorn, Zev ; Trapani, Josef G. ; Liu, Qianyong ; Nicolson, Teresa. / Rabconnectin3α promotes stable activity of the H + pump on synaptic vesicles in hair cells. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 32. pp. 11144-11156.
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