1. Biochemistry and Chemical Biology
  2. Microbiology and Infectious Disease
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Fucosylation and protein glycosylation create functional receptors for cholera toxin

  1. Amberlyn M Wands
  2. Akiko Fujita
  3. Janet E McCombs
  4. Jakob Cervin
  5. Benjamin Dedic
  6. Andrea C Rodriguez
  7. Nicole Nischan
  8. Michelle R Bond
  9. Marcel Mettlen
  10. David C Trudgian
  11. Andrew Lemoff
  12. Marianne Quiding-Järbrink
  13. Bengt Gustavsson
  14. Catharina Steentoft
  15. Henrik Clausen
  16. Hamid Mirzaei
  17. Susann Teneberg
  18. Ulf Yrlid
  19. Jennifer J Kohler  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. University of Gothenburg, Sweden
  3. National Institutes of Health, United States
  4. University of Copenhagen, Denmark
Research Article
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Cite this article as: eLife 2015;4:e09545 doi: 10.7554/eLife.09545

Abstract

Cholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors using its B subunit (CTB). The ganglioside (glycolipid) GM1 is thought to be the sole CT receptor; however, the mechanism by which CTB binding to GM1 mediates internalization of CT remains enigmatic. Here we report that CTB binds cell surface glycoproteins. Relative contributions of gangliosides and glycoproteins to CTB binding depend on cell type, and CTB binds primarily to glycoproteins in colonic epithelial cell lines. Using a metabolically incorporated photocrosslinking sugar, we identified one CTB-binding glycoprotein and demonstrated that the glycan portion of the molecule, not the protein, provides the CTB interaction motif. We further show that fucosylated structures promote CTB entry into a colonic epithelial cell line and subsequent host cell intoxication. CTB-binding fucosylated glycoproteins are present in normal human intestinal epithelia and could play a role in cholera.

Article and author information

Author details

  1. Amberlyn M Wands

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Akiko Fujita

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Janet E McCombs

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jakob Cervin

    Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Benjamin Dedic

    Department of Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. Andrea C Rodriguez

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Nicole Nischan

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Michelle R Bond

    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Marcel Mettlen

    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. David C Trudgian

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Andrew Lemoff

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Marianne Quiding-Järbrink

    Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  13. Bengt Gustavsson

    Department of Surgery, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  14. Catharina Steentoft

    Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  15. Henrik Clausen

    Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  16. Hamid Mirzaei

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Susann Teneberg

    Department of Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenberg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  18. Ulf Yrlid

    Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  19. Jennifer J Kohler

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    jennifer.kohler@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Human subjects: This study was performed according to the Declaration of Helsinki and approved by the Regional Board of Ethics in Medical Research in West Sweden, approval no 249-15. Patients received oral and written information about the study by the study nurse the day before surgery, and if they agreed to participate, they signed a consent form stating permission to use the tissue and publish the results in a way that did not reveal the identity of the donor.

Reviewing Editor

  1. Reid Gilmore, University of Massachusetts Medical School, United States

Publication history

  1. Received: June 19, 2015
  2. Accepted: October 26, 2015
  3. Accepted Manuscript published: October 29, 2015 (version 1)
  4. Version of Record published: December 10, 2015 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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