Vacuolar H+-ATPases (V-ATPases) acidify multiple organelles, and subunit isoforms help impart organelle-specific regulation of acidification. The regulator of ATPase of vacuoles and endosomes (RAVE) complex regulates organelle acidification by promoting V-ATPase assembly. This work demonstrates that RAVE is the first identified isoform-specific V-ATPase assembly factor required for control of vacuolar acidification.

Background:The RAVE complex is required for glucose-sensitive V-ATPase assembly, but its mechanism is unknown. Results: Newly defined RAVE-V-ATPase interactions suggest assembly mechanisms. Conclusion: RAVE shows glucose-sensitive interactions with vacuolar membranes and may help orient V-ATPase subunit C during assembly. Significance: Mammalian rabconnectins likely require similar V-ATPase interactions to support V-ATPase assembly and may be reversibly recruited to membranes.