Abstract
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 Leu262 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.
Highlights
Aquaporins (AQPs) are water-selective channel proteins that allow the rapid movement of water across the plasma membrane in secretory and adsorptive cells [1]
C-Terminal Domain Is Required for Plasma Membrane Localization of AQP5
To determine whether the C-terminal domain of AQP5 is required for its normal localization, we first examined the cellular localization of the hAQP5 mutant that lacks the C-terminal domain (∆CT, Leu225 to Arg265 ) in HEK-293 cells
Summary
Aquaporins (AQPs) are water-selective channel proteins that allow the rapid movement of water across the plasma membrane in secretory and adsorptive cells [1]. Among the 13 AQP isoforms, AQP5 is selectively expressed in the apical membrane of exocrine glands [2]. AQP5 knockout (KO) mice show significant reduction of water secretion from the salivary [3] and submucosal glands [4], indicating the importance of AQP5 for exocrine function. Because the water pores of AQPs do not have a gating function, the amount of cell surface expression of AQP5 is important for its water transport activity. Lipopolysaccharides were shown to increase AQP5 translocalization to the plasma membrane, which is mediated by a p38 MAP kinase-dependent mechanism [10]. Several reports have shown that an increase in intracellular Ca2+ following activation of the M3 acetylcholine receptor stimulates translocation of AQP5 from the intracellular space to the plasma membrane of salivary gland cells [11]. Nitric oxide was shown to decrease the plasma membrane localization of AQP5 via lipid-raft-dependent endocytosis [12]
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