Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions
Purpose of reviewThe 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 to...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2024.1508806/full |
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| author | Dipak Maskey Dipak Maskey Jessica Granados Pineda Jessica Granados Pineda Pablo A. Ortiz Pablo A. Ortiz |
| author_facet | Dipak Maskey Dipak Maskey Jessica Granados Pineda Jessica Granados Pineda Pablo A. Ortiz Pablo A. Ortiz |
| author_sort | Dipak Maskey |
| collection | DOAJ |
| description | Purpose of reviewThe 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.Recent FindingsProtein-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.SummaryHere we review the current understanding of apical trafficking of NKCC2 in the thick ascending limb (TAL) which is tightly controlled by protein-protein interactions, protein turnover and by phosphorylation and dephosphorylation. We discuss new proteins and processes that regulate NKCC2 that have physiological and pathological significance. |
| format | Article |
| id | doaj-art-0cc221a8c54f4fd08e4bde63fdf4c39a |
| institution | Kabale University |
| issn | 1664-042X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj-art-0cc221a8c54f4fd08e4bde63fdf4c39a2024-12-09T06:28:42ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2024-12-011510.3389/fphys.2024.15088061508806Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactionsDipak Maskey0Dipak Maskey1Jessica Granados Pineda2Jessica Granados Pineda3Pablo A. Ortiz4Pablo A. Ortiz5Department of Internal Medicine, Hypertension and Vascular Research Division, Henry ford hospital, Detroit, MI, United StatesDepartment of Physiology, Integrative Bioscience Center, Wayne State University, Detroit, MI, United StatesDepartment of Internal Medicine, Hypertension and Vascular Research Division, Henry ford hospital, Detroit, MI, United StatesDepartment of Physiology, Integrative Bioscience Center, Wayne State University, Detroit, MI, United StatesDepartment of Internal Medicine, Hypertension and Vascular Research Division, Henry ford hospital, Detroit, MI, United StatesDepartment of Physiology, Integrative Bioscience Center, Wayne State University, Detroit, MI, United StatesPurpose of reviewThe 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.Recent FindingsProtein-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.SummaryHere we review the current understanding of apical trafficking of NKCC2 in the thick ascending limb (TAL) which is tightly controlled by protein-protein interactions, protein turnover and by phosphorylation and dephosphorylation. We discuss new proteins and processes that regulate NKCC2 that have physiological and pathological significance.https://www.frontiersin.org/articles/10.3389/fphys.2024.1508806/fullthick ascending limbSLC12A1NKCC2protein-protein interactionsproteomics |
| spellingShingle | Dipak Maskey Dipak Maskey Jessica Granados Pineda Jessica Granados Pineda Pablo A. Ortiz Pablo A. Ortiz Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions Frontiers in Physiology thick ascending limb SLC12A1 NKCC2 protein-protein interactions proteomics |
| title | Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions |
| title_full | Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions |
| title_fullStr | Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions |
| title_full_unstemmed | Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions |
| title_short | Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions |
| title_sort | update on nkcc2 regulation in the thick ascending limb tal by membrane trafficking phosphorylation and protein protein interactions |
| topic | thick ascending limb SLC12A1 NKCC2 protein-protein interactions proteomics |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2024.1508806/full |
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