Rabconnectin3α promotes stable activity of the H+ pump on synaptic vesicles in hair cells.
Rabconnectin3α promotes stable activity of the H+ pump on synaptic vesicles in hair cells.
复制标题
DOI：
10.1523/jneurosci.1705-12.2012
复制
发表时间：
2012-08-08
期刊：
影响因子：
--
通讯作者：
Nicolson T
中科院分区：
文献类型：
--
作者：
Einhorn Z;Trapani JG;Liu Q;Nicolson T
Acidification of synaptic vesicles relies on the Vacuolar-type ATPase (V-ATPase), which 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 where 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.
