Claudin-2-dependent paracellular channels are dynamically gated

  1. Christopher R Weber
  2. Guo Hua Liang
  3. Yitang Wang
  4. Sudipto Das
  5. Le Shen
  6. Alan S L Yu
  7. Deborah J Nelson
  8. Jerrold R Turner  Is a corresponding author
  1. The University of Chicago, United States
  2. Lupin Research Park, India
  3. University of Kansas Medical Center, United States

Abstract

Intercellular tight junctions form selectively permeable barriers that seal the paracellular space. Trans-tight junction flux has been measured across large epithelial surfaces, but conductance across individual channels has never been measured. We report a novel trans-tight junction patch clamp technique that detects flux across individual claudin-2 channels within the tight junction of cultured canine renal tubule or human intestinal epithelial monolayers. In both cells, claudin-2 channels display conductances of ~90 pS. The channels are gated, strictly dependent on claudin-2 expression, and display size- and charge-selectivity typical of claudin-2. Kinetic analyses indicate one open and two distinct closed states. Conductance is symmetrical and reversible, characteristic of a passive, paracellular process, and blocked by reduced temperature or site-directed mutagenesis and chemical derivatization of the claudin-2 pore. We conclude that claudin-2 forms gated paracellular channels and speculate that modulation of tight junction channel gating kinetics may be an unappreciated mechanism of barrier regulation.

Article and author information

Author details

  1. Christopher R Weber

    Department of Pathology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Guo Hua Liang

    Department of Pathology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yitang Wang

    Department of Pathology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sudipto Das

    Lupin Research Park, Pune, India
    Competing interests
    The authors declare that no competing interests exist.
  5. Le Shen

    Department of Pathology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Alan S L Yu

    Division of Nephrology and Hypertension and the Kidney Institute, University of Kansas Medical Center, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Deborah J Nelson

    Department of Pharmacological and Physiological Sciences, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jerrold R Turner

    Department of Pathology, The University of Chicago, Chicago, United States
    For correspondence
    jturner@bsd.uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Fiona M Watt, King's College London, United Kingdom

Version history

  1. Received: July 6, 2015
  2. Accepted: November 12, 2015
  3. Accepted Manuscript published: November 14, 2015 (version 1)
  4. Version of Record published: February 2, 2016 (version 2)

Copyright

© 2015, Weber et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Christopher R Weber
  2. Guo Hua Liang
  3. Yitang Wang
  4. Sudipto Das
  5. Le Shen
  6. Alan S L Yu
  7. Deborah J Nelson
  8. Jerrold R Turner
(2015)
Claudin-2-dependent paracellular channels are dynamically gated
eLife 4:e09906.
https://doi.org/10.7554/eLife.09906

Share this article

https://doi.org/10.7554/eLife.09906

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