Affiliation:
1. Department of Cell Biology, Harvard Medical School and The Center for Blood Research for Biomedical Research, Boston, Massachusetts 02115
2. Gastrointestinal Cell Biology, Department of Pediatrics, Children's Hospital and Harvard Medical School and the Harvard Digestive Diseases Center, Boston, Massachusetts 02115
Abstract
Cholera toxin (CT) and related AB5toxins bind to glycolipids at the plasma membrane and are then transported in a retrograde manner, first to the Golgi and then to the endoplasmic reticulum (ER). In the ER, the catalytic subunit of CT is translocated into the cytosol, resulting in toxicity. Using fluorescence microscopy, we found that CT is internalized by multiple endocytic pathways. Inhibition of the clathrin-, caveolin-, or Arf6-dependent pathways by overexpression of appropriate dominant mutants had no effect on retrograde traffic of CT to the Golgi and ER, and it did not affect CT toxicity. Unexpectedly, when we blocked all three endocytic pathways at once, although fluorescent CT in the Golgi and ER became undetectable, CT-induced toxicity was largely unaffected. These results are consistent with the existence of an additional retrograde pathway used by CT to reach the ER.
Publisher
American Society for Cell Biology (ASCB)
Subject
Cell Biology,Molecular Biology
Cited by
87 articles.
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