title: Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV.
abstract: 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.
authors.affiliation: INSERM, Unité 1193, F-94800 Villejuif, France.|University of Paris-Sud, UMR-S 1193, F-94800 Villejuif, France.|Laboratoire des Hépatites Virales, Département de Virologie. Institut Pasteur du Maroc, BP 20360 Casablanca, Maroc.|Faculté des Sciences, Laboratoire de Biochimie-Immunologie, Univ. Mohammed V, Rabat, Maroc.
authors.forename: Abdellah
authors.initials: A
authors.lastname: Akil
authors.affiliation: INSERM, Unité 1193, F-94800 Villejuif, France.|University of Paris-Sud, UMR-S 1193, F-94800 Villejuif, France.|DHU Hepatinov, Villejuif F-94800, France.
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.affiliation: INSERM, Unité 1193, F-94800 Villejuif, France.|University of Paris-Sud, UMR-S 1193, F-94800 Villejuif, France.|DHU Hepatinov, Villejuif F-94800, France.
authors.forename: Mohyeddine
authors.initials: M
authors.lastname: Omrane
authors.affiliation: INSERM U1183, Institute of Regenerative Medicine and Biotherapy, University of Montpellier, 34295 Montpellier, France.|Department of Hepato-Gastroenterology A, Hospital Saint Eloi, CHRU, 34295 Montpellier, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Gondeau
authors.affiliation: University of Paris-Sud, -UFR medecine- INSERM UMS33, Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Desterke
authors.affiliation: INSERM, Unité 1193, F-94800 Villejuif, France.|University of Paris-Sud, UMR-S 1193, F-94800 Villejuif, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Marin
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Tronchère
authors.affiliation: Virologie Moléculaire et Structurale CNRS UPR 3296 - INRA UsC 1358, 91198 Gif-sur-Yvette, France.
authors.forename: Cyntia
authors.initials: C
authors.lastname: Taveneau
authors.affiliation: INSERM, Unité 1193, F-94800 Villejuif, France.|University of Paris-Sud, UMR-S 1193, F-94800 Villejuif, France.
authors.forename: Sokhavuth
authors.initials: S
authors.lastname: Sar
authors.affiliation: INSERM U1183, Institute of Regenerative Medicine and Biotherapy, University of Montpellier, 34295 Montpellier, France.|Department of Hepato-Gastroenterology A, Hospital Saint Eloi, CHRU, 34295 Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Briolotti
authors.affiliation: Laboratoire des Hépatites Virales, Département de Virologie. Institut Pasteur du Maroc, BP 20360 Casablanca, Maroc.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Benjelloun
authors.affiliation: Faculté des Sciences, Laboratoire de Biochimie-Immunologie, Univ. Mohammed V, Rabat, Maroc.|Univ. Internationale de Rabat, Sala Al Jadida, Maroc.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Benjouad
authors.affiliation: INSERM U1183, Institute of Regenerative Medicine and Biotherapy, University of Montpellier, 34295 Montpellier, France.|Department of Hepato-Gastroenterology A, Hospital Saint Eloi, CHRU, 34295 Montpellier, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Maurel
authors.affiliation: Institut Pasteur, 75724 Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Thiers
authors.affiliation: Virologie Moléculaire et Structurale CNRS UPR 3296 - INRA UsC 1358, 91198 Gif-sur-Yvette, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bressanelli
authors.affiliation: INSERM, Unité 1193, F-94800 Villejuif, France.|University of Paris-Sud, UMR-S 1193, F-94800 Villejuif, France.|DHU Hepatinov, Villejuif F-94800, France.|AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: INSERM, Unité 1193, F-94800 Villejuif, France.|University of Paris-Sud, UMR-S 1193, F-94800 Villejuif, France.|Institut Pasteur, 75724 Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Bréchot
authors.affiliation: INSERM, Unité 1193, F-94800 Villejuif, France.|University of Paris-Sud, UMR-S 1193, F-94800 Villejuif, France.|DHU Hepatinov, Villejuif F-94800, France.
authors.forename: Ama
authors.initials: A
authors.lastname: Gassama-Diagne
mesh_terms: D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000472:pathogenicity* / Q000502:physiology; D006526:Hepatitis C / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D066292:Lipid Droplets / Q000187:drug effects / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000821:virology; D008870:Microtubules / Q000378:metabolism* / Q000821:virology; D019301:Oleic Acid / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D058112:Septins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D018129:Phosphatidylinositol Phosphates; C113567:phosphatidylinositol 5-phosphate; D019301:Oleic Acid; C013173:osteum; C474315:SEPTIN9 protein, human; D058112:Septins