C-Terminal Domain of Aquaporin-5 Is Required to Pass Its Protein Quality Control and Ensure Its Trafficking to Plasma Membrane

Aquaporin-5 (AQP5) is selectively expressed in the apical membrane of exocrine glands, such as salivary, lacrimal, and submucosal glands. It is important for the secretory function of exocrine glands because mice with the knockout of AQP5 exhibit a significant reduction in secretion from these glands. Previous reports indicated that the AQP5 C-terminal domain is crucial for the localization of AQP5 at the plasma membrane, but it remains unclear which motif or amino acid residues in the C-terminal domain are essential for this. In this study, we examined the effects of various AQP5 C-terminal deletions or mutations on the expression of AQP5 on the cell surface. AQP5 C-terminal domain mutants did not localize on the plasma membrane, and Leu(262) was shown to be crucial for AQP5′s plasma membrane localization. The mutants localized in the autophagosome or lysosome and showed decreased protein stability via lysosomal degradation. Taking these findings together, our study suggests that the C-terminal domain is required for AQP5 to pass protein quality control and be trafficked to the plasma membrane.