Our laboratory is focused on understanding the structure, mechanism, and regulation of the vacuolar family (H+)-ATPases (or V-ATPases). The V-ATPases are ATP-dependent proton pumps which function in the acidification of intracellular compartments and play an important role in such processes as receptor-mediated endocytosis, intracellular membrane traffic, and viral entry. V-ATPases at the plasma membrane also function in pH homeostasis, bone resorption and tumor metastasis. A crucial question we are addressing is how cells are able to regulate the activity of V-ATPases present in different cellular membranes.