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Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site
Open accessAbstract
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.
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Cites
Phenomenological Theory of Ion Solvation. Effective Radii of Hydrated Ions
Nightingale, E. R. (1959) · The Journal of Physical Chemistry · doi:10.1021/j150579a011 · Cited by 3,505
Cation selective glass electrodes and their mode of operation
Eisenman, G. (1962) · Biophysical Journal · doi:10.1016/s0006-3495(62)86959-8 · Cited by 852
Cited by
Intestinal mucosal barrier function in health and disease
Turner, J. R. (2009) · Nature reviews. Immunology · doi:10.1038/nri2653 · Cited by 3,952
Claudins and the Modulation of Tight Junction Permeability
Günzel, D., & Yu, A. S. L. (2013) · Physiological Reviews · doi:10.1152/physrev.00019.2012 · Cited by 1,456
Self-citationThe intestinal epithelial barrier: a therapeutic target?
Odenwald, M. A., & Turner, J. R. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.169 · Cited by 1,288
Physiology and function of the tight junction
Anderson, J. M., & Van Itallie, C. M. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a002584 · Cited by 1,059
Tight Junction Pore and Leak Pathways: A Dynamic Duo
Shen, L., Weber, C. R., Raleigh, D. R., Yu, D., & Turner, J. R. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-012110-142150 · Cited by 872
Metadata
- Authors
- Yu, A. S. L., Cheng, M. H., Angelow, S., Günzel, D., Kanzawa, S. A., Schneeberger, E. E., Fromm, M., & Coalson, R. D.
- Venue
- The Journal of General Physiology
- Publisher
- Rockefeller University Press
- Published
- 2008-12-29
- Volume
- 133
- Issue
- 1
- Pages
- 111-127
- ISSN
- 0022-1295 (ISSN-L)
- 1540-7748
- OpenAlex
- W2102015799
- Cited by
- 310
- References
- 2
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site. https://app.cochat.ai/papers/10.1085/jgp.200810154
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- Yu, A. S. L., Cheng, M. H., Angelow, S., Günzel, D., Kanzawa, S. A., Schneeberger, E. E., Fromm, M., & Coalson, R. D. (2009). Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site. The Journal of General Physiology. https://doi.org/10.1085/jgp.200810154
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