Format

Send to

Choose Destination
Sci Rep. 2019 Feb 28;9(1):3021. doi: 10.1038/s41598-019-39702-4.

Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia.

Author information

1
Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
2
Institute of Clinical Medicine Research of Bucheon St. Mary's Hospital, Bucheon, Korea.
3
Integrative Research Support Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
4
Division of Nephrology, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Korea.
5
Department of Anatomy, Ewha Womans University School of Medicine, Seoul, Korea.
6
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
7
Severance Biomedical Science Institute, College of Medicine, Yonsei University, Seoul, Korea.
8
Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea. drkimyk@catholic.ac.kr.
9
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. drkimyk@catholic.ac.kr.
10
Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea. jinkim@catholic.ac.kr.

Abstract

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 (Atg7Δpc) mice. In hypokalemic Atg7-floxed (Atg7f/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 Atg7Δpc 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 Atg7f/f and Atg7Δpc 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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center