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The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2
NKCC and KCC transporters mediate coupled transport of Na(+)+K(+)+Cl(−) and K(+)+Cl(−) across the plasma membrane, thus regulating cell Cl(−) concentration and cell volume and playing critical roles in transepithelial salt and water transport and in neuronal excitability. The function of these trans...
| Autores principales: | , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889885/ https://www.ncbi.nlm.nih.gov/pubmed/33597714 http://dx.doi.org/10.1038/s42003-021-01750-w |
| _version_ | 1783652395519049728 |
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| author | Zhang, Sensen Zhou, Jun Zhang, Yuebin Liu, Tianya Friedel, Perrine Zhuo, Wei Somasekharan, Suma Roy, Kasturi Zhang, Laixing Liu, Yang Meng, Xianbin Deng, Haiteng Zeng, Wenwen Li, Guohui Forbush, Biff Yang, Maojun |
| author_facet | Zhang, Sensen Zhou, Jun Zhang, Yuebin Liu, Tianya Friedel, Perrine Zhuo, Wei Somasekharan, Suma Roy, Kasturi Zhang, Laixing Liu, Yang Meng, Xianbin Deng, Haiteng Zeng, Wenwen Li, Guohui Forbush, Biff Yang, Maojun |
| author_sort | Zhang, Sensen |
| collection | PubMed |
| description | NKCC and KCC transporters mediate coupled transport of Na(+)+K(+)+Cl(−) and K(+)+Cl(−) across the plasma membrane, thus regulating cell Cl(−) concentration and cell volume and playing critical roles in transepithelial salt and water transport and in neuronal excitability. The function of these transporters has been intensively studied, but a mechanistic understanding has awaited structural studies of the transporters. Here, we present the cryo-electron microscopy (cryo-EM) structures of the two neuronal cation-chloride cotransporters human NKCC1 (SLC12A2) and mouse KCC2 (SLC12A5), along with computational analysis and functional characterization. These structures highlight essential residues in ion transport and allow us to propose mechanisms by which phosphorylation regulates transport activity. |
| format | Online Article Text |
| id | pubmed-7889885 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-78898852021-03-03 The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2 Zhang, Sensen Zhou, Jun Zhang, Yuebin Liu, Tianya Friedel, Perrine Zhuo, Wei Somasekharan, Suma Roy, Kasturi Zhang, Laixing Liu, Yang Meng, Xianbin Deng, Haiteng Zeng, Wenwen Li, Guohui Forbush, Biff Yang, Maojun Commun Biol Article NKCC and KCC transporters mediate coupled transport of Na(+)+K(+)+Cl(−) and K(+)+Cl(−) across the plasma membrane, thus regulating cell Cl(−) concentration and cell volume and playing critical roles in transepithelial salt and water transport and in neuronal excitability. The function of these transporters has been intensively studied, but a mechanistic understanding has awaited structural studies of the transporters. Here, we present the cryo-electron microscopy (cryo-EM) structures of the two neuronal cation-chloride cotransporters human NKCC1 (SLC12A2) and mouse KCC2 (SLC12A5), along with computational analysis and functional characterization. These structures highlight essential residues in ion transport and allow us to propose mechanisms by which phosphorylation regulates transport activity. Nature Publishing Group UK 2021-02-17 /pmc/articles/PMC7889885/ /pubmed/33597714 http://dx.doi.org/10.1038/s42003-021-01750-w Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Zhang, Sensen Zhou, Jun Zhang, Yuebin Liu, Tianya Friedel, Perrine Zhuo, Wei Somasekharan, Suma Roy, Kasturi Zhang, Laixing Liu, Yang Meng, Xianbin Deng, Haiteng Zeng, Wenwen Li, Guohui Forbush, Biff Yang, Maojun The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2 |
| title | The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2 |
| title_full | The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2 |
| title_fullStr | The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2 |
| title_full_unstemmed | The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2 |
| title_short | The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2 |
| title_sort | structural basis of function and regulation of neuronal cotransporters nkcc1 and kcc2 |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889885/ https://www.ncbi.nlm.nih.gov/pubmed/33597714 http://dx.doi.org/10.1038/s42003-021-01750-w |
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