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

doi:10.7554/eLife.09545

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

Glycomics Program

41 Citations (Scopus)

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 language	English
Article number	e09545
Journal	eLife
Volume	4
Pages (from-to)	1-38
Number of pages	38
ISSN	2050-084X
DOIs	https://doi.org/10.7554/eLife.09545
Publication status	Published - 29 Oct 2015

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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, 1-38. [e09545 ]. https://doi.org/10.7554/eLife.09545

Wands, AM, Fujita, A, McCombs, JE, Cervin, J, Dedic, B, Rodriguez, AC, Nischan, N, Bond, MR, Mettlen, M, Trudgian, DC, Lemoff, A, Quiding-Järbrink, M, Gustavsson, B, Steentoft, C, Clausen, H, Mirzaei, H, Teneberg, S, Yrlid, U & Kohler, JJ 2015, 'Fucosylation and protein glycosylation create functional receptors for cholera toxin', eLife, vol. 4, e09545 , pp. 1-38. https://doi.org/10.7554/eLife.09545

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title = "Fucosylation and protein glycosylation create functional receptors for cholera toxin",

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.",

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

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T1 - Fucosylation and protein glycosylation create functional receptors for cholera toxin

AU - Wands, Amberlyn M

AU - Fujita, Akiko

AU - McCombs, Janet E

AU - Cervin, Jakob

AU - Dedic, Benjamin

AU - Rodriguez, Andrea C

AU - Nischan, Nicole

AU - Bond, Michelle R

AU - Mettlen, Marcel

AU - Trudgian, David C

AU - Lemoff, Andrew

AU - Quiding-Järbrink, Marianne

AU - Gustavsson, Bengt

AU - Steentoft, Catharina

AU - Clausen, Henrik

AU - Mirzaei, Hamid

AU - Teneberg, Susann

AU - Yrlid, Ulf

AU - Kohler, Jennifer J

PY - 2015/10/29

Y1 - 2015/10/29

N2 - 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.

AB - 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.

U2 - 10.7554/eLife.09545

DO - 10.7554/eLife.09545

M3 - Journal article

C2 - 26512888

SN - 2050-084X

VL - 4

SP - 1

EP - 38

JO - eLife

JF - eLife

M1 - e09545

ER -

Fucosylation and protein glycosylation create functional receptors for cholera toxin

Abstract

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