Fucosylation and protein glycosylation create functional receptors for cholera toxin
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 re...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/09545 |
| id |
doaj-3c68ba7482ae44199ba3d13b04350700 |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Fucosylation and protein glycosylation create functional receptors for cholera toxin eLife glycoprotein glycolipids/gangliosides endocytosis cholera epithelial cell toxins |
| author_facet |
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 |
| author_sort |
Amberlyn M Wands |
| title |
Fucosylation and protein glycosylation create functional receptors for cholera toxin |
| title_short |
Fucosylation and protein glycosylation create functional receptors for cholera toxin |
| title_full |
Fucosylation and protein glycosylation create functional receptors for cholera toxin |
| title_fullStr |
Fucosylation and protein glycosylation create functional receptors for cholera toxin |
| title_full_unstemmed |
Fucosylation and protein glycosylation create functional receptors for cholera toxin |
| title_sort |
fucosylation and protein glycosylation create functional receptors for cholera toxin |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2015-10-01 |
| description |
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. |
| topic |
glycoprotein glycolipids/gangliosides endocytosis cholera epithelial cell toxins |
| url |
https://elifesciences.org/articles/09545 |
| work_keys_str_mv |
AT amberlynmwands fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT akikofujita fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT janetemccombs fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT jakobcervin fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT benjamindedic fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT andreacrodriguez fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT nicolenischan fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT michellerbond fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT marcelmettlen fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT davidctrudgian fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT andrewlemoff fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT mariannequidingjarbrink fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT bengtgustavsson fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT catharinasteentoft fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT henrikclausen fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT hamidmirzaei fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT susannteneberg fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT ulfyrlid fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin AT jenniferjkohler fucosylationandproteinglycosylationcreatefunctionalreceptorsforcholeratoxin |
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doaj-3c68ba7482ae44199ba3d13b043507002021-05-05T00:05:15ZengeLife Sciences Publications LtdeLife2050-084X2015-10-01410.7554/eLife.09545Fucosylation and protein glycosylation create functional receptors for cholera toxinAmberlyn M Wands0Akiko Fujita1Janet E McCombs2Jakob Cervin3https://orcid.org/0000-0002-3840-1008Benjamin Dedic4Andrea C Rodriguez5Nicole Nischan6Michelle R Bond7Marcel Mettlen8David C Trudgian9Andrew Lemoff10Marianne Quiding-Järbrink11Bengt Gustavsson12Catharina Steentoft13Henrik Clausen14Hamid Mirzaei15Susann Teneberg16Ulf Yrlid17Jennifer J Kohler18https://orcid.org/0000-0001-5373-3329Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Surgery, University of Gothenburg, Gothenburg, SwedenCopenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkCopenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Department of Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesCholera 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.https://elifesciences.org/articles/09545glycoproteinglycolipids/gangliosidesendocytosischoleraepithelial celltoxins |