| RRC ID |
88386
|
| 著者 |
Kim WY, Nam SA, Choi A, Kim YM, Park SH, Kim HL, Kim H, Han KH, Yang CW, Lee MS, Kim YK, Kim J.
|
| タイトル |
Atg7-dependent canonical autophagy regulates the degradation of aquaporin 2 in prolonged hypokalemia.
|
| ジャーナル |
Sci Rep
|
| 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.
|
| 巻・号 |
9(1)
|
| ページ |
3021
|
| 公開日 |
2019-2-28
|
| DOI |
10.1038/s41598-019-39702-4
|
| PII |
10.1038/s41598-019-39702-4
|
| PMID |
30816234
|
| PMC |
PMC6395725
|
| MeSH |
Animals
Aquaporin 2 / metabolism*
Autophagy / physiology*
Autophagy-Related Protein 7 / metabolism*
Down-Regulation / physiology
Hypokalemia / metabolism*
Kidney / metabolism
Male
Mice
Microtubule-Associated Proteins / metabolism
Phosphorylation / physiology
rab GTP-Binding Proteins / metabolism
|
| IF |
3.998
|
| リソース情報 |
| 実験動物マウス |
RBRC00806 |
