Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV
| Autor: | Mickaël Marin, Abdelaziz Benjouad, Abdellah Akil, Sokhavuth Sar, Soumaya Benjelloun, Christian Bréchot, Cyntia Taveneau, Didier Samuel, Claire Gondeau, Philippe Briolotti, Valérie Thiers, Mohyeddine Omrane, Christophe Desterke, Stéphane Bressanelli, Hélène Tronchère, Patrick Maurel, Juan Peng, Ama Gassama-Diagne |
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| Přispěvatelé: | Institut Pasteur du Maroc, Réseau International des Instituts Pasteur (RIIP), Laboratoire de biochimie et Immunologie, Faculté des Sciences, Université Mohammed V de Rabat [Agdal] (UM5), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hepatinov (DHU), Université Paris-Sud - Paris 11 (UP11)-Centre Hépato-Biliaire Paul Brousse, Service d'Hépatogastroentérologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique (CNRS), Université Internationale de Rabat (UIR), Institut Pasteur [Paris] (IP), A.A. was supported by a fellowship of RII Pasteur, University of Paris XI and CHB association. C.G. was supported by a grant from Agence nationale de recherches sur le sida et les hépatites virales (ANRS). This work was supported by a grant from Association pour la Recherche sur le Cancer (ARC/SUBV/CKLQ6) to AGD, Houel, Ludivine, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Mohammed V de Rabat [Agdal], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pasteur [Paris] |
| Rok vydání: | 2016 |
| Předmět: |
Liver Cirrhosis
0301 basic medicine General Physics and Astronomy Hepacivirus Virus Replication Septin Microtubules Phosphatidylinositol Phosphates [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Lipid droplet Cytoskeleton Multidisciplinary cytoskeleton phosphoinositides Hepatitis C Hedgehog signaling pathway 3. Good health Cell biology diacylglycerol acyltransferase-1 Host-Pathogen Interactions [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases biological phenomena cell phenomena and immunity replication Science cell regulation yeast septin macromolecular substances Biology hepatitis-c virus Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Downregulation and upregulation Microtubule Cell Line Tumor core protein Humans Phosphatidylinositol 5-phosphate fungi biogenesis metabolism [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology Lipid Droplets General Chemistry Lipid Metabolism [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology eye diseases 030104 developmental biology Gene Expression Regulation Septins Biogenesis Oleic Acid |
| Zdroj: | Nature Communications, Vol 7, Iss 1, Pp 1-19 (2016) Nature Communications Nature Communications, 2016, 7, ⟨10.1038/ncomms12203⟩ Nature Communications (7), . (2016) Nature Communications, Nature Publishing Group, 2016, 7, ⟨10.1038/ncomms12203⟩ |
| ISSN: | 2041-1723 |
| Popis: | The accumulation of lipid droplets (LD) is frequently observed in hepatitis C virus (HCV) infection and represents an important risk factor for the development of liver steatosis and cirrhosis. The mechanisms of LD biogenesis and growth remain open questions. Here, transcriptome analysis reveals a significant upregulation of septin 9 in HCV-induced cirrhosis compared with the normal liver. HCV infection increases septin 9 expression and induces its assembly into filaments. Septin 9 regulates LD growth and perinuclear accumulation in a manner dependent on dynamic microtubules. The effects of septin 9 on LDs are also dependent on binding to PtdIns5P, which, in turn, controls the formation of septin 9 filaments and its interaction with microtubules. This previously undescribed cooperation between PtdIns5P and septin 9 regulates oleate-induced accumulation of LDs. Overall, our data offer a novel route for LD growth through the involvement of a septin 9/PtdIns5P signalling pathway. The accumulation of lipid droplets is often observed in hepatitis C virus infection, but the mechanism of their formation is not known. Here the authors show that septin 9 expression is increased in infected livers, and a septin 9/phosphatidylinositol 5-phosphate signalling pathway regulates the growth of lipid droplets. |
| Databáze: | OpenAIRE |
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