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PMID: 19114638 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Molecular basis for cation selectivity in claudin-2-based paracellular pores: identification of an electrostatic interaction site.

The Journal of general physiology ·Vol. 133 ·No. 1 ·2009-01-00 ·Pages 111-27

Yu AS, Cheng MH, Angelow S, Günzel D, Kanzawa SA, Schneeberger EE, Fromm M, Coalson RD

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Cations/metabolism Cell Membrane Permeability Cells, Cultured Claudins Computer Simulation Dogs Ion Channels/chemistry,genetics,metabolism Kinetics Membrane Proteins/chemistry,genetics,metabolism Mice Models, Biological Molecular Sequence Data Mutation Protein Isoforms/genetics,metabolism Sequence Alignment Static Electricity
Chemicals
Cations Claudins Cldn2 protein, mouse Ion Channels Membrane Proteins Protein Isoforms
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Yu Alan S L
Division of Nephrology, Department of Medicine,University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA. [email protected]
Cheng Mary H
Angelow Susanne
Günzel Dorothee
Kanzawa Sanae A
Schneeberger Eveline E
Fromm Michael
Coalson Rob D
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Article Info
Journal
The Journal of general physiology
Abbr.
J Gen Physiol
ISSN
1540-7748
DOI
10.1085/jgp.200810154
Email
[email protected]
Published
2009-01-00
Pages
111-27
Language
English
Region
United States
NLM ID
2985110R
PMCID
PMC2606938
Subset
IM
Grants
NIDDK NIH HHS · R01 DK062283 · United States
NHLBI NIH HHS · HL25822 · United States
NIDDK NIH HHS · DK48522 · United States
NIDDK NIH HHS · DK062283 · United States
NIDDK NIH HHS · P30 DK048522 · United States
NHLBI NIH HHS · R01 HL025822 · United States
External Links
PubMed source DOI: 10.1085/jgp.200810154 PMC Full Text View journal details
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