Exploring the Link between Vacuolar-Type Proton ATPase and Epithelial Cell Polarity

Vacuolar-type H⁺-ATPase (V-ATPase) was first identified as an electrogenic proton pump that acidifies the lumen of intracellular organelles. Subsequently, it was observed that the proton pump also participates in the acidification of extracellular compartments. V-ATPase plays important roles in a wide range of cell biological processes and physiological functions by generating an acidic pH; therefore, it has attracted much attention not only in basic research but also in pathological and clinical aspects. Emerging evidence indicates that the luminal acidic endocytic organelles and their trafficking may function as important hubs that connect and coordinate various signaling pathways. Various pharmacological analyses have suggested that acidic endocytic organelles are important for the maintenance of cell polarity. Recently, several studies using genetic approaches have revealed the involvement of V-ATPase in the establishment and maintenance of apico-basal polarity. This review provides a brief overview of the relationship between the polarity of epithelial cells and V-ATPase as well as V-ATPase driven luminal acidification.