Institution: | 1 GI Cell Biology, Children's Hospital and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA 2 Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA |
Abstract: | Cholera toxin (CT) and related AB5-subunit toxins move from the plasma membrane through the trans-Golgi and endoplasmic reticulum (ER) to the cytosol of host cells. The toxins exploit a specific glycolipid pathway rather than a protein pathway. They bind glycolipids that associate with lipid rafts at the cell surface, which carry the toxins retrograde to the Golgi and ER. In the ER, the A1-chain of the CT unfolds and enters the cytosol by hijacking the cellular machinery that enables misfolded proteins to cross the membrane for degradation by the proteasome, a process termed retro-translocation. Upon entering the cytosol, the A1-chain rapidly refolds, avoids the proteasome and induces toxicity. |