Regulation of V-ATPase Expression in Mammalian Cells

Vacuolar ATPases (V-ATPases) are large multisubunit complexes that actively transport protons across cellular membranes to acidify intracellular compartments, thereby serving a critical housekeeping function. In addition, V-ATPases are also expressed on the plasma membrane of cell types such as kidney epithelia and osteoclasts, which require high levels of proton secretion to perform their specialized activities. This multiplicity of function is achieved by the expression of numerous V-ATPase subunit isoforms that are mixed and matched to produce complexes required for each cellular activity. Multiple regulatory mechanisms are necessary to allow coordinated expression of V-ATPase subunit proteins involved in both housekeeping and specialized functions. This review will summarize studies during the last two decades that have revealed transcriptional and post-transcriptional controls that govern expression of V-ATPase subunits. These studies are beginning to elucidate overarching mechanisms that permit coordinated expression of ubiquitous subunits while directing tissue-specific expression of others.