{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T15:51:39Z","timestamp":1793634699109,"version":"4.5.1"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,9,7]],"date-time":"2010-09-07T00:00:00Z","timestamp":1283817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2010,9,7]],"date-time":"2010-09-07T00:00:00Z","timestamp":1283817600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK048373"],"award-info":[{"award-number":["DK048373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:p>\n                    <jats:italic>Vibrio cholerae<\/jats:italic>\n                    \u2010derived zonula occludins toxin (Zot) is a multifunctional protein that reversibly disassembles intestinal tight junctions (tjs). Zot structure\u2010function analysis has mapped this activity to aa 288\u2013293, named AT1002. AT1002 reduced transepithelial electrical resistance across rat small intestine,\n                    <jats:italic>ex vivo,<\/jats:italic>\n                    as did Zot and its processed mature form, \u0394G. AT1002 increased\n                    <jats:italic>in vivo<\/jats:italic>\n                    permeability to sugar tracers, whereas scrambled control peptides did not. Binding and barrier assays in proteinase activated receptor (PAR)\n                    <jats:sub>2<\/jats:sub>\n                    \u2010expressing and PAR\n                    <jats:sub>2<\/jats:sub>\n                    \u2010null cells established AT1002 activity to be PAR\n                    <jats:sub>2<\/jats:sub>\n                    dependent. Coincident with the increased intestinal permeability, confocal microscopy of AT1002\u2010exposed rat intestinal IEC6 cells revealed displacement of ZO\u20101 and occludin from intercellular boundaries. In coimmunoprecipitation assays, AT1002 decreased ZO\u20101\u2010occludin and ZO\u20101\u2010claudin 1 interactions coincident with PKC\u03b1\u2010dependent ZO\u20101 serine\/threonine phosphorylation. Further, AT1002 increased serine phosphorylation of myosin 1C and, at the same time, transiently diminished its association with ZO\u20101. The COOH\u2010terminal domain of ZO\u20101 was required for its association with myosin 1C. These data indicate that the NH\n                    <jats:sub>2<\/jats:sub>\n                    \u2010terminal portion of active Zot contains a PAR\n                    <jats:sub>2<\/jats:sub>\n                    \u2010activating motif, FCIGRL, that increases PKC\u03b1\u2010dependent ZO\u20101 and myosin 1C serine\/threonine phosphorylation. These modifications provoke selective disengagement of ZO\u20101 from its binding partners, occludin, claudin 1, and myosin 1C, coincident with opening of tjs.\u2014Goldblum, S. E., Rai, U., Tripathi, A., Thakar, M., De Leo, L., Di Toro, N., Not, T., Ramachandran, R., Puche, A. C., Hollenberg, M. D., Fasano, A. The active Zot domain (aa 288\u2013293) increases ZO\u20101 and myosin 1C serine\/ threonine phosphorylation, alters interaction between ZO\u20101 and its binding partners, and induces tight junction disassembly through proteinase activated receptor 2 activation.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 144\u2013158 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.10-158972","type":"journal-article","created":{"date-parts":[[2010,9,17]],"date-time":"2010-09-17T23:03:17Z","timestamp":1284764597000},"page":"144-158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["The active Zot domain (aa 288\u2013293) increases ZO\u20101 and myosin 1C serine\/threonine phosphorylation, alters interaction between ZO\u20101 and its binding partners, and induces tight junction disassembly through proteinase activated receptor 2 activation"],"prefix":"10.1096","volume":"25","author":[{"given":"Simeon E.","family":"Goldblum","sequence":"first","affiliation":[{"name":"Mucosal Biology Research Center University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usha","family":"Rai","sequence":"additional","affiliation":[{"name":"Mucosal Biology Research Center University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Mucosal Biology Research Center University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjusha","family":"Thakar","sequence":"additional","affiliation":[{"name":"Mucosal Biology Research Center University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigina","family":"De Leo","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Development Science University of Trieste Trieste Italy"},{"name":"Children Hospital Istituto di Recovero e Cura a Carattere Scientifico Burlo Garofolo Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Di Toro","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Development Science University of Trieste Trieste Italy"},{"name":"Children Hospital Istituto di Recovero e Cura a Carattere Scientifico Burlo Garofolo Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarcisio","family":"Not","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Development Science University of Trieste Trieste Italy"},{"name":"Children Hospital Istituto di Recovero e Cura a Carattere Scientifico Burlo Garofolo Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rithwik","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics and Department of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam C.","family":"Puche","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morley D.","family":"Hollenberg","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Fasano","sequence":"additional","affiliation":[{"name":"Mucosal Biology Research Center University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,9,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-36673-3"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.12.5242"},{"key":"e_1_2_6_4_1","first-page":"19160","article-title":"Zonula occlu\u2010dens toxin structure\u2010function analysis. 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