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Cholera Toxin: An Intracellular Journey into the Cytosol by Way of the Endoplasmic Reticulum
GI Cell Biology, Children's Hospital (and Harvard Medical School), 300 Longwood Avenues, Enders 720, Boston, MA 02115, USA
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
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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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.
Wernick 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.
Wernick, 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.