Fucosylation and protein glycosylation create functional receptors for cholera toxin

Amberlyn M. Wands, Akiko Fujita, Janet E. McCombs, Jakob Cervin, Benjamin Dedic, Andrea C. Rodriguez, Nicole Nischan, Michelle R. Bond, Marcel Mettlen, David C. Trudgian, Andrew Lemoff, Marianne Quiding-Järbrink, Bengt Gustavsson, Catharina Steentoft, Henrik Clausen, Hamid Mirzaei, Susann Teneberg, Ulf Yrlid, Jennifer J. Kohler

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Article numbere09545
JournaleLife
Volume4
Issue numberOCTOBER2015
DOIs
StatePublished - Oct 29 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

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    Wands, A. M., Fujita, A., McCombs, J. E., Cervin, J., Dedic, B., Rodriguez, A. C., Nischan, N., Bond, M. R., Mettlen, M., Trudgian, D. C., Lemoff, A., Quiding-Järbrink, M., Gustavsson, B., Steentoft, C., Clausen, H., Mirzaei, H., Teneberg, S., Yrlid, U., & Kohler, J. J. (2015). Fucosylation and protein glycosylation create functional receptors for cholera toxin. eLife, 4(OCTOBER2015), [e09545]. https://doi.org/10.7554/eLife.09545