Revisiting the NaCl cotransporter regulation by with-no-lysine kinases

American Journal of Physiology. Cell Physiology
Silvana Bazúa-Valenti, Gerardo Gamba

Abstract

The renal thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) is the salt transporter in the distal convoluted tubule. Its activity is fundamental for defining blood pressure levels. Decreased NCC activity is associated with salt-remediable arterial hypotension with hypokalemia (Gitelman disease), while increased activity results in salt-sensitive arterial hypertension with hyperkalemia (pseudohypoaldosteronism type II; PHAII). The discovery of four different genes causing PHAII revealed a complex multiprotein system that regulates the activity of NCC. Two genes encode for with-no-lysine (K) kinases WNK1 and WNK4, while two encode for kelch-like 3 (KLHL3) and cullin 3 (CUL3) proteins that form a RING type E3 ubiquitin ligase complex. Extensive research has shown that WNK1 and WNK4 are the targets for the KLHL3-CUL3 complex and that WNKs modulate the activity of NCC by means of intermediary Ste20-type kinases known as SPAK or OSR1. The understanding of the effect of WNKs on NCC is a complex issue, but recent evidence discussed in this review suggests that we could be reaching the end of the dark ages regarding this matter.

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Citations

Feb 11, 2016·Annual Review of Physiology·Juliette HadchouelGerardo Gamba
May 15, 2016·Molecular and Cellular Endocrinology·Reinhold G Erben
Jul 7, 2016·Journal of the American Society of Nephrology : JASN·Martin J WolleyMichael Stowasser
Sep 14, 2016·Bone·Reinhold G Erben, Olena Andrukhova
May 19, 2017·American Journal of Physiology. Renal Physiology·Lena L RosenbaekRobert A Fenton
Feb 17, 2017·Physiology·Alicia A McDonough, Jang H Youn
Nov 4, 2017·Toxicologic Pathology·Reinhold G Erben
May 31, 2018·American Journal of Physiology. Renal Physiology·Eduardo R ArgaizGerardo Gamba
Sep 29, 2018·Channels·Hila WardakJenny Van Der Wijst
Aug 9, 2018·American Journal of Physiology. Renal Physiology·Mauricio Ostrosky-FridGerardo Gamba
Dec 19, 2018·Journal of the American Society of Nephrology : JASN·Peng WuDao-Hong Lin
Jan 6, 2017·Journal of the American Society of Nephrology : JASN·Catherina A CuevasWen-Hui Wang
Oct 15, 2019·American Journal of Physiology. Renal Physiology·Alissa A FrameRichard D Wainford
Dec 17, 2019·American Journal of Physiology. Renal Physiology·Hyun-Wook LeeI David Weiner
Jun 21, 2016·Current Opinion in Nephrology and Hypertension·Eduardo R Argaiz, Gerardo Gamba
Apr 22, 2016·American Journal of Physiology. Renal Physiology·Silvana Bazúa-ValentiGerardo Gamba
Jun 27, 2019·Journal of the American Society of Nephrology : JASN·Peng WuDao-Hong Lin
Apr 17, 2020·Journal of the American Society of Nephrology : JASN·Peng WuDao-Hong Lin
Feb 12, 2020·The Journal of Experimental Biology·Sabine L LaguëWilliam K Milsom

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