Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 Nature Publishing Group
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160003
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s41598-019-39702-4
- PubMed https://pubmed.ncbi.nlm.nih.gov/30816234
초록/요약
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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