Gangliosides That Associate with Lipid Rafts Mediate Transport of Cholera and Related Toxins from the Plasma Membrane to Endoplasmic Reticulm
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- Yukako Fujinaga
- GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
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- Anne A. Wolf
- GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
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- Chiara Rodighiero
- GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
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- Heidi Wheeler
- GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
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- Billy Tsai
- Cell Biology, Harvard Medical School, Boston, Massachusetts 02115
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- Larry Allen
- GI Cell Biology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
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- Michael G. Jobling
- Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80262
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- Tom Rapoport
- Cell Biology, Harvard Medical School, Boston, Massachusetts 02115
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- Randall K. Holmes
- Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80262
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- 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>
収録刊行物
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- Molecular Biology of the Cell
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Molecular Biology of the Cell 14 (12), 4783-4793, 2003-12
American Society for Cell Biology (ASCB)
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詳細情報
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- CRID
- 1363388843737469440
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- NII論文ID
- 30018378774
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- ISSN
- 19394586
- 10591524
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- データソース種別
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