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Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia
- Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia
- Kim W.-Y.; Nam S.A.; Choi A.; Kim Y.-M.; Park S.H.; Kim H.L.; Kim H.; Han K.-H.; Yang C.W.; Lee M.-S.; Kim Y.K.; Kim J.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Scientific Reports
- Scientific Reports vol. 9, no. 1
- Nature Publishing Group
- SCIE; SCOPUS
- Document Type
- Prolonged hypokalemia induces a decrease of urinary concentrating ability via down-regulation of aquaporin 2 (AQP2); however, the precise mechanisms remain unknown. To investigate the role of autophagy in the degradation of AQP2, we generated the principal cell-specific Atg7 deletion (Atg7 Δpc ) mice. In hypokalemic Atg7-floxed (Atg7 f/f ) mice, huge irregular shaped LC3-positive autophagic vacuoles accumulated mainly in inner medullary collecting duct (IMCD) cells. Total- and pS261-AQP2 were redistributed from apical and subapical domains into these vacuoles, which were not co-localized with RAB9. However, in the IMCD cells of hypokalemic Atg7 Δpc mice, these canonical autophagic vacuoles were markedly reduced, whereas numerous small regular shaped LC3-negative/RAB9-positive non-canonical autophagic vacuoles were observed along with diffusely distributed total- and pS261-AQP2 in the cytoplasm. The immunoreactivity of pS256-AQP2 in the apical membrane of IMCD cells was markedly decreased, and no redistribution was observed in both hypokalemic Atg7 f/f and Atg7 Δpc mice. These findings suggest that AQP2 down regulation in hypokalemia was induced by reduced phosphorylation of AQP2, resulting in a reduction of apical plasma labeling of pS256-AQP2 and degradation of total- and pS261-AQP2 via an LC3/ATG7-dependent canonical autophagy pathway. © 2019, The Author(s).
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