V0-ATPase downregulation induces MVID-like brush border defects independently of apical trafficking in the mammalian intestine
| Autor: | Aurélien Bidaud-Meynard, Ophélie Nicolle, Anne Bourdais, Maela Duclos, Jad Saleh, Frank Ruemmele, Henner F Farin, Delphine Delacour, Despina Moshous, Grégoire Michaux |
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| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institute for Tumor Biology and Experimental Therapy [Frankfurt, Germany], German Cancer Consortium [Heidelberg] (DKTK), Goethe-University Frankfurt am Main |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | BioRxiv BioRxiv, 2022, ⟨10.1101/2022.11.04.515188⟩ |
| ISSN: | 2692-8205 |
| Popis: | SummaryIntestinal microvillus atrophy is a major cause of enteropathies such as idiopathic or congenital diarrhea that are often associated with severe morbidity. It can be caused by genetic disorders, inflammatory diseases, toxins or pathogens. In particular, Microvillus inclusion disease (MVID) is characterized by a chronic intractable diarrhea and a severe microvillus atrophy. It is triggered by mutations inMYO5B, STX3, MUNC18.2orUNC45Awhich alter epithelial polarity by affecting apical trafficking in intestinal epithelial cells. Furthermore, we recently established that the depletion of the V0sector of the V-ATPase complex induces an MVID-like phenotype inC. elegans. In this study we investigated the function of the V0-ATPase complex in mouse intestinal organoids. We found that its depletion also triggers a very severe microvillus atrophy in this model. Furthermore, we established that the polarity of intestinal cells is affected in a patient carrying mutations inTCIRG1which encodes a V0-ATPase subunit. However, V0- ATPase depletion does not recapitulate other MVID-specific phenotypes such as subapical vesicle accumulation and Rab11+ endosomes mislocalization. Finally, we found that the apical localization of the V0-ATPase is disrupted in MVID patients. Altogether these results suggest a role for the V0-ATPase in microvillus atrophy which might be independent from apical trafficking. |
| Databáze: | OpenAIRE |
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