Descending thin limb of the intermediate loop expresses both aquaporin 1 and urea transporter A2 in the mouse kidney

Kim, Wan-Young; Lee, Hyun‐Wook; Han, Ki-Hwan; Nam, Sun-Ah; Choi, Arum; Kim, Yong-Kyun; Kim, Jin

doi:10.1007/s00418-016-1434-7

Cited by 13 publications

(7 citation statements)

References 26 publications

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“…Ultrathin sections were cut and photographed using a JEOL JEM-1010 transmission electron microscope. The precise method was as described in a previous report 69 .…”

Section: Methodsmentioning

confidence: 99%

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

Kim

Nam

Choi

et al. 2019

Sci Rep

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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.

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“…Ultrathin sections were cut and photographed using a JEOL JEM-1010 transmission electron microscope. The precise method was as described in a previous report 69 .…”

Section: Methodsmentioning

confidence: 99%

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

Kim

Nam

Choi

et al. 2019

Sci Rep

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“…UT-A1, UT-A3, and UT-A4 (only in rat) are expressed on the plasma membrane of principle cells at the end of inner medullary collecting duct (IMCD) (9)(10)(11)(12)(13)(14). UT-A2 is localized in the lower half of the thin descending limb of Henle's loops in short-looped nephrons and in the initial inner medulla (IM) segments of the thin descending limb in long-looped nephrons (7,(15)(16)(17). UT-B, the only member derived from gene Slc14a1, is expressed in renal descending vasa recta and multiple extrarenal tissues (18)(19)(20)(21)(22)(23)(24).…”

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confidence: 99%

The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism

Geng

Zhang

et al. 2020

Journal of Biological Chemistry

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Urea transporters are a family of urea-selective channel proteins expressed in multiple tissues that play an important role in the urine-concentrating mechanism of the mammalian kidney. Previous studies have shown that knockout of urea transporter (UT)-B, UT-A1/A3, or all UTs leads to urea-selective diuresis, indicating that urea transporters have important roles in urine concentration. Here, we sought to determine the role of UT-A1 in the urine-concentrating mechanism in a newly developed UT-A1–knockout mouse model. Phenotypically, daily urine output in UT-A1–knockout mice was nearly 3-fold that of WT mice and 82% of all-UT–knockout mice, and the UT-A1–knockout mice had significantly lower urine osmolality than WT mice. After 24-h water restriction, acute urea loading, or high-protein (40%) intake, UT-A1–knockout mice were unable to increase urine-concentrating ability. Compared with all-UT–knockout mice, the UT-A1–knockout mice exhibited similarly elevated daily urine output and decreased urine osmolality, indicating impaired urea-selective urine concentration. Our experimental findings reveal that UT-A1 has a predominant role in urea-dependent urine-concentrating mechanisms, suggesting that UT-A1 represents a promising diuretic target.

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“…The “lower DTL” segments, which are also present in both the outer medulla (OM) and IM, do not express detectable AQP1 and include both long‐looped DTLs and descending segments that have been recently defined in the mouse as the intermediate loop DTLs (Kim et al. ).…”

Section: Resultsmentioning

confidence: 99%

“…These tubules express AQP1 and have a high water permeability unlike short‐loop descending thin limbs (Kim et al. ). Previous studies have also provided support for a countercurrent ammonia recycling system in the OM.…”

Section: Discussionmentioning

confidence: 99%

Expression of SLC 4A11 protein in mouse and rat medulla: a candidate transporter involved in outer medullary ammonia recycling

2019

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SLC 4A11 is a multifunctional membrane transporter involved with H + transport, NH 3 and alkaline pH stimulated H + transport, and water transport. The role of SLC 4A11 in the kidney is not well understood. A prior study has shown that in murine kidney, SLC 4A11/LacZ staining is primarily in the long‐looped descending thin limb ( DTL ) as determined by colocalization with aquaporin 1 ( AQP 1), a protein that is expressed in some, but not all, descending thin limb segments. Using a previously characterized polyclonal antibody, we demonstrate the selective expression of SLC 4A11 in the upper DTL s (which are AQP 1‐positive) in the outer medulla and inner medulla with little or no expression in the lower DTL s (which are AQP ‐1‐null). SLC 4A11 also colocalized with AQP 1 and the urea transporter UT ‐B in the mouse descending vasa recta, but was absent in mouse and rat ascending vasa recta. Mouse, but not rat, outer medullary collecting duct cells also labeled for SLC 4A11. Our results are compatible with the hypothesis that in the inner stripe of the outer medulla, SLC 4A11 plays a role in the countercurrent transport of ammonia absorbed from the outer medullary thick ascending limb and secreted into the long‐looped DTL s. SLC 4A11 can potentially modulate the rate of ammonia transport in the mouse outer medullary collecting duct. Our data suggest functionally unique SLC 4A11 pathways in mouse and rat and complement previous studies of DTL Na + , urea and water permeability indicating that the upper and lower DTL s of long‐looped nephrons are functionally distinct.

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Descending thin limb of the intermediate loop expresses both aquaporin 1 and urea transporter A2 in the mouse kidney

Cited by 13 publications

References 26 publications

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

The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism

Expression of SLC 4A11 protein in mouse and rat medulla: a candidate transporter involved in outer medullary ammonia recycling

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