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Cholera toxin toxicity does not require functional Arf6- and dynamin-dependent endocytic pathways.

ABSTRACT: Cholera toxin (CT) and related AB(5) toxins 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.

SUBMITTER: Massol RH

PROVIDER: S-EPMC491824 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature

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Cholera toxin toxicity does not require functional Arf6- and dynamin-dependent endocytic pathways.

Massol Ramiro H RH Larsen Jakob E JE Fujinaga Yukako Y Lencer Wayne I WI Kirchhausen Tomas T

Molecular biology of the cell 20040514 8

Cholera toxin (CT) and related AB(5) toxins 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 ...[more]

PMID: 15146065

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