Regulation of V‐ATPase trafficking in neurons by Rab GTPases

Redistribution of acid‐base transporters is a crucial regulatory mechanism for many cells to cope with extracellular pH changes. Moreover, in the central nervous system, rapid pH shifts occur during neuronal activity. However, the specific proteins involved in regulated vesicular traffic of acid‐base transporters in neurons are largely unknown. In the present study we have investigated the impact of members of the Rab family of small GTPases on the trafficking of the vacuolar‐type H + ‐ATPase (V‐ATPase) in neurons in vitro using primary hippocampal cells from mouse embryonic day 18.5 as an experimental model. We show differential co‐localization and interaction of V‐ATPase with Rab family members. Extracellular acidosis causes translocation of the V‐ATPase from the Golgi apparatus toward the dendrites and the plasma membrane, a process mediated by Rab GTPases. Loss‐of‐function experiments using specific siRNA against distinct Rab family members prevent acidosis‐induced V‐ATPase translocation. The data introduce members of the Rab family as crucial regulators of acidosis‐induced V‐ATPase traffic in neuronal cells. Funded by the Deutsche Forschungsgemeinschaft.