Cholera toxin: an intracellular journey into the cytosol by way of the endoplasmic reticulum
Cholera toxin (CT), an AB(5)-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 is...
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Veröffentlicht in: | Toxins 2010-03, Vol.2 (3), p.310-325 |
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creator | Wernick, Naomi L B Chinnapen, Daniel J-F Cho, Jin Ah Lencer, Wayne I |
description | Cholera toxin (CT), an AB(5)-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. |
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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. 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Here, we review the mechanisms of toxin trafficking by GM1 and retro-translocation of the A1-chain to the cytosol.</description><subject>Adenosine diphosphate</subject><subject>Cell Membrane - metabolism</subject><subject>Cholera Toxin - chemistry</subject><subject>Cholera Toxin - metabolism</subject><subject>Cytosol - metabolism</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>G(M1) Ganglioside - metabolism</subject><subject>Humans</subject><subject>Protein Conformation</subject><subject>Protein Transport</subject><subject>Review</subject><subject>Toxins</subject><subject>Translocation</subject><subject>Waterborne diseases</subject><issn>2072-6651</issn><issn>2072-6651</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpVkc1LwzAYxoMobswdvUrAczUfbdN4EGT4BQMvehNCmqSuI21m0qr9780-lC2X5H3y43m_ADjH6IpSjq4791O3gSCKKEZHYEwQI0meZ_h47z0C0xCWKB5KMcfsFIwIQTnPinwM3mcLZ42XcGN1A2UL67bzUhlreys9XLret2ZYqw52CwPV0LngLCwH-C0H6KqNalrtVlaGplbQm65Wve2bM3BSSRvMdHdPwNvD_evsKZm_PD7P7uaJSnHaJRXRjNMsLzKOsMGEFJqyrJCEF1zFqCp0mZZaalVinhrMClxmEnFdmrxiNKUTcLv1XfVlY7Qy6w6sWPm6kX4QTtbi8KetF-LDfQmKszgSGg0udwbeffYmdGLTdqxZRILxlHHOIpVsKeVdCN5U_xkwEut9iIN9RP5iv6x_-m_69BdYLIjv</recordid><startdate>20100301</startdate><enddate>20100301</enddate><creator>Wernick, Naomi L B</creator><creator>Chinnapen, Daniel J-F</creator><creator>Cho, Jin Ah</creator><creator>Lencer, Wayne I</creator><general>MDPI AG</general><general>Molecular Diversity Preservation International</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T7</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PATMY</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>5PM</scope></search><sort><creationdate>20100301</creationdate><title>Cholera toxin: an intracellular journey into the cytosol by way of the endoplasmic reticulum</title><author>Wernick, Naomi L B ; 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subjects | Adenosine diphosphate Cell Membrane - metabolism Cholera Toxin - chemistry Cholera Toxin - metabolism Cytosol - metabolism Endoplasmic Reticulum - metabolism G(M1) Ganglioside - metabolism Humans Protein Conformation Protein Transport Review Toxins Translocation Waterborne diseases |
title | Cholera toxin: an intracellular journey into the cytosol by way of the endoplasmic reticulum |
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