The intracellular voyage of cholera toxin: going retro.
Cholera toxin (CT) and related AB(5)-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.
Lencer
Wayne I
WI
GI Cell Biology, Children's Hospital and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. wayne.lencer@tch.harvard.edu
Tsai
Billy
B
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular
D002772:Cholera Toxin