title: Ganglioside GM1-mediated transcytosis of cholera toxin bypasses the retrograde pathway and depends on the structure of the ceramide domain.
abstract: Cholera toxin causes diarrheal disease by binding ganglioside GM1 on the apical membrane of polarized intestinal epithelial cells and trafficking retrograde through sorting endosomes, the trans-Golgi network (TGN), and into the endoplasmic reticulum. A fraction of toxin also moves from endosomes across the cell to the basolateral plasma membrane by transcytosis, thus breeching the intestinal barrier. Here we find that sorting of cholera toxin into this transcytotic pathway bypasses retrograde transport to the TGN. We also find that GM1 sphingolipids can traffic from apical to basolateral membranes by transcytosis in the absence of toxin binding but only if the GM1 species contain cis-unsaturated or short acyl chains in the ceramide domain. We found previously that the same GM1 species are needed to efficiently traffic retrograde into the TGN and endoplasmic reticulum and into the recycling endosome, implicating a shared mechanism of action for sorting by lipid shape among these pathways.
authors.affiliation: From the Division of Gastroenterology, Boston Children's Hospital,; Harvard Digestive Diseases Center, and; Harvard Medical School, Boston, Massachusetts, 02115. Electronic address: david.saslowsky@childrens.harvard.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Saslowsky
authors.affiliation: From the Division of Gastroenterology, Boston Children's Hospital,; Harvard Medical School, Boston, Massachusetts, 02115.
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Te Welscher
authors.affiliation: From the Division of Gastroenterology, Boston Children's Hospital,; Harvard Medical School, Boston, Massachusetts, 02115.
authors.forename: Daniel J-F
authors.initials: DJ
authors.lastname: Chinnapen
authors.affiliation: From the Division of Gastroenterology, Boston Children's Hospital,; Harvard Digestive Diseases Center, and.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Wagner
authors.affiliation: From the Division of Gastroenterology, Boston Children's Hospital.
authors.forename: Joy
authors.initials: J
authors.lastname: Wan
authors.affiliation: From the Division of Gastroenterology, Boston Children's Hospital.
authors.forename: Eli
authors.initials: E
authors.lastname: Kern
authors.affiliation: From the Division of Gastroenterology, Boston Children's Hospital,; Harvard Digestive Diseases Center, and; Harvard Medical School, Boston, Massachusetts, 02115.
authors.forename: Wayne I
authors.initials: WI
authors.lastname: Lencer
mesh_terms: D000818:Animals; D002518:Ceramides / Q000235:genetics / Q000378:metabolism*; D002772:Cholera Toxin / Q000378:metabolism* / Q000494:pharmacology*; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000235:genetics / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D057900:Transcytosis / Q000187:drug effects*
chemical_list: D002518:Ceramides; D005677:G(M1) Ganglioside; D002772:Cholera Toxin
keywords: Cell Biology; Cholera Toxin; Endosomes; Ganglioside; Intracellular Trafficking; Lipid Transport; Membrane Lipids; Membrane Trafficking; Polarized Epithelia; Sphingolipid