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Toxins 2010, 2(3), 310-325; doi:10.3390/toxins2030310
Review
Cholera Toxin: An Intracellular Journey into the Cytosol by Way of the Endoplasmic Reticulum
1
GI Cell Biology, Children's Hospital (and Harvard Medical School), 300 Longwood Avenues, Enders 720, Boston, MA 02115, USA
2
The Harvard Digestive Diseases Center, Boston, MA 02115, USA
* Author to whom correspondence should be addressed.
Received: 27 January 2010; in revised form: 27 February 2010 / Accepted: 2 March 2010 / Published: 5 March 2010
(This article belongs to the Special Issue Enterotoxins)
Abstract: Cholera toxin (CT), an AB5-subunit toxin, enters host cells by binding the ganglioside GM1 at the plasma membrane (PM) and travels retrograde through the trans-Golgi Network into the endoplasmic reticulum (ER). In the ER, a portion of CT, the enzymatic A1-chain, is unfolded by protein disulfide isomerase and retro-translocated to the cytosol by hijacking components of the ER associated degradation pathway for misfolded proteins. After crossing the ER membrane, the A1-chain refolds in the cytosol and escapes rapid degradation by the proteasome to induce disease by ADP-ribosylating the large G-protein Gs and activating adenylyl cyclase. Here, we review the mechanisms of toxin trafficking by GM1 and retro-translocation of the A1-chain to the cytosol.
Keywords: cholera toxin; retro-translocation; ERAD; retrograde pathway; lipid rafts
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MDPI and ACS Style
Wernick, N.L.B.; Chinnapen, D.-F.; Cho, J.A.; Lencer, W.I. Cholera Toxin: An Intracellular Journey into the Cytosol by Way of the Endoplasmic Reticulum. Toxins 2010, 2, 310-325.
AMA StyleWernick NLB, Chinnapen D-F, Cho JA, Lencer WI. Cholera Toxin: An Intracellular Journey into the Cytosol by Way of the Endoplasmic Reticulum. Toxins. 2010; 2(3):310-325.
Chicago/Turabian StyleWernick, Naomi L. B.; Chinnapen, Daniel J.-F.; Cho, Jin Ah; Lencer, Wayne I. 2010. "Cholera Toxin: An Intracellular Journey into the Cytosol by Way of the Endoplasmic Reticulum." Toxins 2, no. 3: 310-325.
