Regulation of synaptic vesicle acidification at the neuronal synapse

The vacuolar H⁺ -adenosine triphosphatases (vATPases) acidify multiple intracellular organelles, including synaptic vesicles (SVs) and secretory granules. Acidification of SVs represents a critical point during the SV cycle: without acidification, neurotransmitters cannot be loaded into SVs. Despite the obvious importance of the vesicle acidification process for neurotrasmission and the life of complex organisms, little is known about the regulation of vATPase at the neuronal synapse. In addition, the composition of the vATPase complex on the SVs is unclear. Here, we summarize the key features of vATPase found on SVs, and propose a model of how vATPase activity is regulated during the SV cycle. It is anticipated that the information from the SV lumen is communicated to SV surface in order to signal successful acidification and neurotransmitter loading: we postulate here that the regulators of the vATPase activity exist (e.g., Rabconnectin-3) that promote the recruitment of SV peripheral proteins and, consequently, SV fusion.