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Review
. 2022 Sep 1;31(5):471-478.
doi: 10.1097/MNH.0000000000000820. Epub 2022 Jul 15.

WNK1 in the kidney

Jessica Paola Bahena-Lopez  1   2 , Gerardo Gamba  1   2   3 , María Castañeda-Bueno  1
Affiliations
Review

WNK1 in the kidney

Jessica Paola Bahena-Lopez et al. Curr Opin Nephrol Hypertens. .

Abstract

Purpose of review: The aim of this manuscript was to review recent evidence uncovering the roles of the With No lysine (K) kinase 1 (WNK1) in the kidney.

Recent findings: Analyses of microdissected mouse nephron segments have revealed the abundance of long-WNK1 and kidney-specific-WNK1 transcripts in different segments. The low levels of L-WNK1 transcripts in the distal convoluted tubule (DCT) stand out and support functional evidence on the lack of L-WNK1 activity in this segment. The recent description of familial hyperkalaemic hypertension (FHHt)-causative mutations affecting the acidic domain of WNK1 supports the notion that KS-WNK1 activates the Na+:Cl- cotransporter NCC. The high sensitivity of KS-WNK1 to KLHL3-targeted degradation and the low levels of L-WNK1 in the DCT, led to propose that this type of FHHt is mainly due to increased KS-WNK1 protein in the DCT. The observation that KS-WNK1 renal protein expression is induced by low K+ diet and recent reassessment of the phenotype of KS-WNK1-/- mice suggested that KS-WNK1 may be necessary to achieve maximal NCC activation under this condition. Evidences on the regulation of other renal transport proteins by WNK1 are also summarized.

Summary: The diversity of WNK1 transcripts in the kidney has complicated the interpretation of experimental data. Integration of experimental data with the knowledge of isoform abundance in renal cell types is necessary in future studies about WNK1 function in the kidney.

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References

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