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Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site
Paracellular ion transport in epithelia is mediated by pores formed by members of the claudin family. The degree of selectivity and the molecular mechanism of ion permeation through claudin pores are poorly understood. By expressing a high-conductance claudin isoform, claudin-2, in high-resistance M...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606938/ https://www.ncbi.nlm.nih.gov/pubmed/19114638 http://dx.doi.org/10.1085/jgp.200810154 |
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author | Yu, Alan S.L. Cheng, Mary H. Angelow, Susanne Günzel, Dorothee Kanzawa, Sanae A. Schneeberger, Eveline E. Fromm, Michael Coalson, Rob D. |
author_facet | Yu, Alan S.L. Cheng, Mary H. Angelow, Susanne Günzel, Dorothee Kanzawa, Sanae A. Schneeberger, Eveline E. Fromm, Michael Coalson, Rob D. |
author_sort | Yu, Alan S.L. |
collection | PubMed |
description | Paracellular ion transport in epithelia is mediated by pores formed by members of the claudin family. The degree of selectivity and the molecular mechanism of ion permeation through claudin pores are poorly understood. By expressing a high-conductance claudin isoform, claudin-2, in high-resistance Madin-Darby canine kidney cells under the control of an inducible promoter, we were able to quantitate claudin pore permeability. Claudin-2 pores were found to be narrow, fluid filled, and cation selective. Charge selectivity was mediated by the electrostatic interaction of partially dehydrated permeating cations with a negatively charged site within the pore that is formed by the side chain carboxyl group of aspartate-65. Thus, paracellular pores use intrapore electrostatic binding sites to achieve a high conductance with a high degree of charge selectivity. |
format | Text |
id | pubmed-2606938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-26069382009-07-01 Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site Yu, Alan S.L. Cheng, Mary H. Angelow, Susanne Günzel, Dorothee Kanzawa, Sanae A. Schneeberger, Eveline E. Fromm, Michael Coalson, Rob D. J Gen Physiol Articles Paracellular ion transport in epithelia is mediated by pores formed by members of the claudin family. The degree of selectivity and the molecular mechanism of ion permeation through claudin pores are poorly understood. By expressing a high-conductance claudin isoform, claudin-2, in high-resistance Madin-Darby canine kidney cells under the control of an inducible promoter, we were able to quantitate claudin pore permeability. Claudin-2 pores were found to be narrow, fluid filled, and cation selective. Charge selectivity was mediated by the electrostatic interaction of partially dehydrated permeating cations with a negatively charged site within the pore that is formed by the side chain carboxyl group of aspartate-65. Thus, paracellular pores use intrapore electrostatic binding sites to achieve a high conductance with a high degree of charge selectivity. The Rockefeller University Press 2009-01 /pmc/articles/PMC2606938/ /pubmed/19114638 http://dx.doi.org/10.1085/jgp.200810154 Text en © 2009 Yu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Articles Yu, Alan S.L. Cheng, Mary H. Angelow, Susanne Günzel, Dorothee Kanzawa, Sanae A. Schneeberger, Eveline E. Fromm, Michael Coalson, Rob D. Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site |
title | Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site |
title_full | Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site |
title_fullStr | Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site |
title_full_unstemmed | Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site |
title_short | Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site |
title_sort | molecular basis for cation selectivity in claudin-2–based paracellular pores: identification of an electrostatic interaction site |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606938/ https://www.ncbi.nlm.nih.gov/pubmed/19114638 http://dx.doi.org/10.1085/jgp.200810154 |
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