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REVIEW article

Front. Physiol.
Sec. Renal Physiology and Pathophysiology
Volume 15 - 2024 | doi: 10.3389/fphys.2024.1508806
This article is part of the Research Topic Regulation and Pathophysiology of Epithelial Transport of the Thick Ascending Limb of the Loop of Henle View all articles

Update on NKCC2 regulation in the Thick Ascending Limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions

Provisionally accepted
DIPAK MASKEY DIPAK MASKEY 1,2Jessica Granados Pineda Jessica Granados Pineda 1,2Pablo A Ortiz Pablo A Ortiz 1,2*
  • 1 Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan, United States
  • 2 Department of Physiology, School of Medicine, Wayne State University, Detroit, Michigan, United States

The final, formatted version of the article will be published soon.

    The thick ascending limb (TAL) of loop of Henle is essential for NaCl, calcium and magnesium homeostasis, pH balance and for urine concentration. NKCC2 is the main transporter for NaCl reabsorption in the TAL and its regulation is very complex. There have been recent advancements toward understanding how NKCC2 is regulated by protein trafficking, protein-protein interaction, and phosphorylation/dephosphorylation. Here, we update the latest molecular mechanisms and players that control NKCC2 function, which gives an increasingly complex picture of NKKC2 regulation in the apical membrane of the TAL.Protein-protein interactions are required as a regulatory mechanism in many cellular processes.A handful of proteins have been recently identified as an interacting partner of NKCC2, which play major roles in regulating NKCC2 trafficking and activity. New players in NKCC2 internalization and trafficking have been identified. NKCC2 activity is also regulated by kinases and phosphatases, and there have been developments in that area as well.

    Keywords: thick ascending limb, SLC12A1, NKCC2, protein-protein interactions, Proteomics

    Received: 09 Oct 2024; Accepted: 22 Nov 2024.

    Copyright: © 2024 MASKEY, Granados Pineda and Ortiz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Pablo A Ortiz, Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.