{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:36:12Z","timestamp":1791264972042,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,8]],"date-time":"2015-12-08T00:00:00Z","timestamp":1449532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-10-INSB-04-01"],"award-info":[{"award-number":["ANR-10-INSB-04-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology of the Cell"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background information<\/jats:title><jats:p>Microvillus inclusion disease (MVID) is a genetic disorder affecting intestinal absorption. It is caused by mutations in <jats:italic>MYO5B<\/jats:italic> or syntaxin 3 (<jats:italic>STX3<\/jats:italic>) affecting apical membrane trafficking. Morphologically, MVID is characterised by a depletion of apical microvilli and the formation of microvillus inclusions inside the cells, suggesting a loss of polarity. To investigate this hypothesis, we examined the location of essential apical polarity determinants in five MVID patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that the polarity determinants Cdc42, Par6B, PKC\u03b6\/\u03b9 and the structural proteins ezrin and phospho\u2010ezrin were lost from the apical membrane and accumulated either in the cytoplasm or on the basal side of enterocytes in patients, which suggests an inversion of cell polarity. Moreover, microvilli\u2010like structures were observed at the basal side as per electron microscopy analysis. We next performed Myo5B depletion in three dimensional grown human Caco2 cells forming cysts and found a direct link between the loss of Myo5B and the mislocalisation of the same apical proteins; furthermore, we observed that a majority of cysts displayed an inverted polarity phenotype as seen in some patients. Finally, we found that this loss of polarity was specific for MVID: tissue samples of patients with Myo5B\u2010independent absorption disorders showed normal polarity but we identified Cdc42 as a potentially essential biomarker for trichohepatoenteric syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that the loss of Myo5B induces a strong loss of enterocyte polarity, potentially leading to polarity inversion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our results show that polarity determinants could be useful markers to help establishing a diagnosis in patients. Furthermore, they could be used to characterise other rare intestinal absorption diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/boc.201500034","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T08:45:01Z","timestamp":1446540301000},"page":"19-28","source":"Crossref","is-referenced-by-count":32,"title":["The localisation of the apical Par\/Cdc42 polarity module is specifically affected in microvillus inclusion disease"],"prefix":"10.1111","volume":"108","author":[{"given":"Gr\u00e9goire","family":"Michaux","sequence":"first","affiliation":[{"name":"CNRS, UMR6290 Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes  F\u201035043 Rennes France"},{"name":"UEB, SFR Biosit, Facult\u00e9 de M\u00e9decine University of Rennes 1  F\u201035043 Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Massey\u2010Harroche","sequence":"additional","affiliation":[{"name":"CNRS, UMR 7288, Developmental Biology Institute of Marseille (IBDM) Aix\u2010Marseille Universit\u00e9  13288 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oph\u00e9lie","family":"Nicolle","sequence":"additional","affiliation":[{"name":"CNRS, UMR6290 Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes  F\u201035043 Rennes France"},{"name":"UEB, SFR Biosit, Facult\u00e9 de M\u00e9decine University of Rennes 1  F\u201035043 Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Rabant","sequence":"additional","affiliation":[{"name":"Pathology Department H\u00f4pital Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Brousse","sequence":"additional","affiliation":[{"name":"Pathology Department H\u00f4pital Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Goulet","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit H\u00f4pital Necker\u2010Enfants Malades  AP\u2010HP Paris France"},{"name":"Sorbonne Paris Cit\u00e9 Universit\u00e9 Paris Descartes  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Le Bivic","sequence":"additional","affiliation":[{"name":"CNRS, UMR 7288, Developmental Biology Institute of Marseille (IBDM) Aix\u2010Marseille Universit\u00e9  13288 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank M.","family":"Ruemmele","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit H\u00f4pital Necker\u2010Enfants Malades  AP\u2010HP Paris France"},{"name":"Sorbonne Paris Cit\u00e9 Universit\u00e9 Paris Descartes  Paris France"},{"name":"Institut Imagine  INSERM U1163 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0854.2000.010111.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2635"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71471"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep12312"},{"issue":"1","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1242\/jcs.107.1.213","article-title":"Differential expression of sucrase\u2010isomaltase in clones isolated from early and late passages of the cell line Caco\u20102: evidence for glucose\u2010dependent negative regulation","volume":"107","author":"Chantret I.","year":"1994","journal-title":"J. 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