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

Scientific Reports
Wan-Young KimJin Kim

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 p...Continue Reading

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Citations

Mar 23, 2021·American Journal of Physiology. Renal Physiology·Lama Al-QusairiPaul A Welling
Jul 28, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qiaojuan LiuChunling Li
Sep 3, 2021·Neural Regeneration Research·Tian-Hao LiYu-Ru Luo

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Methods Mentioned

BETA
ubiquitination
Electron
electron microscopy
transmission electron microscopy
light microscopy

Software Mentioned

STAT

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