Gangliosides That Associate with Lipid Rafts Mediate Transport of Cholera and Related Toxins from the Plasma Membrane to Endoplasmic Reticulm

  • Yukako Fujinaga
    GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
  • Anne A. Wolf
    GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
  • Chiara Rodighiero
    GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
  • Heidi Wheeler
    GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
  • Billy Tsai
    Cell Biology, Harvard Medical School, Boston, Massachusetts 02115
  • Larry Allen
    GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
  • Michael G. Jobling
    Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80262
  • Tom Rapoport
    Cell Biology, Harvard Medical School, Boston, Massachusetts 02115
  • Randall K. Holmes
    Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80262
  • Wayne I. Lencer
    GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115

抄録

<jats:p>Cholera toxin (CT) travels from the plasma membrane of intestinal cells to the endoplasmic reticulum (ER) where a portion of the A-subunit, the A1 chain, crosses the membrane into the cytosol to cause disease. A related toxin, LTIIb, binds to intestinal cells but does not cause toxicity. Here, we show that the B-subunit of CT serves as a carrier for the A-subunit to the ER where disassembly occurs. The B-subunit binds to gangliosides in lipid rafts and travels with the ganglioside to the ER. In many cells, LTIIb follows a similar pathway, but in human intestinal cells it binds to a ganglioside that fails to associate with lipid rafts and it is sorted away from the retrograde pathway to the ER. Our results explain why LTIIb does not cause disease in humans and suggest that gangliosides with high affinity for lipid rafts may provide a general vehicle for the transport of toxins to the ER.</jats:p>

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詳細情報

  • CRID
    1363388843737469440
  • NII論文ID
    30018378774
  • DOI
    10.1091/mbc.e03-06-0354
  • ISSN
    19394586
    10591524
  • データソース種別
    • Crossref
    • CiNii Articles

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