{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:47:15Z","timestamp":1792741635845,"version":"4.5.0"},"reference-count":82,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2010,3,5]],"date-time":"2010-03-05T00:00:00Z","timestamp":1267747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/toxins2030310","type":"journal-article","created":{"date-parts":[[2010,3,8]],"date-time":"2010-03-08T11:22:08Z","timestamp":1268047328000},"page":"310-325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":194,"title":["Cholera Toxin: An Intracellular Journey into the Cytosol by Way of the Endoplasmic Reticulum"],"prefix":"10.3390","volume":"2","author":[{"given":"Naomi L. B.","family":"Wernick","sequence":"first","affiliation":[{"name":"GI Cell Biology, Children's Hospital (and Harvard Medical School), 300 Longwood Avenues, Enders 720, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.-F.","family":"Chinnapen","sequence":"additional","affiliation":[{"name":"GI Cell Biology, Children's Hospital (and Harvard Medical School), 300 Longwood Avenues, Enders 720, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Ah","family":"Cho","sequence":"additional","affiliation":[{"name":"GI Cell Biology, Children's Hospital (and Harvard Medical School), 300 Longwood Avenues, Enders 720, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne I.","family":"Lencer","sequence":"additional","affiliation":[{"name":"GI Cell Biology, Children's Hospital (and Harvard Medical School), 300 Longwood Avenues, Enders 720, Boston, MA 02115, USA"},{"name":"The Harvard Digestive Diseases Center, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2010,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/S0092-8674(01)00289-6","article-title":"Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin","volume":"104","author":"Tsai","year":"2001","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1083\/jcb.153.3.529","article-title":"Rapid cycling of lipid raft markers between the cell surface and Golgi complex","volume":"153","author":"Nichols","year":"2001","journal-title":"J. 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