Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV

Abdellah Akil, Juan Peng, Mohyeddine Omrane, Claire Gondeau, Christophe Desterke, Mickaël Marin, Hélène Tronchère, Cyntia Taveneau, Sokhavuth Sar, Philippe Briolotti, Soumaya Benjelloun, Abdelaziz Benjouad, Patrick Maurel, Valérie Thiers, Stéphane Bressanelli, Didier Samuel, Christian Bréchot and Ama Gassama-Diagne ()
Additional contact information
Abdellah Akil: INSERM
Juan Peng: INSERM
Mohyeddine Omrane: INSERM
Claire Gondeau: INSERM U1183, Institute of Regenerative Medicine and Biotherapy, University of Montpellier
Christophe Desterke: University of Paris-Sud, -UFR medecine- INSERM UMS33
Mickaël Marin: INSERM
Hélène Tronchère: INSERM U1048, I2MC and Université Paul Sabatier
Cyntia Taveneau: Virologie Moléculaire et Structurale CNRS UPR 3296 - INRA UsC 1358
Sokhavuth Sar: INSERM
Philippe Briolotti: INSERM U1183, Institute of Regenerative Medicine and Biotherapy, University of Montpellier
Soumaya Benjelloun: Laboratoire des Hépatites Virales
Abdelaziz Benjouad: Faculté des Sciences, Laboratoire de Biochimie-Immunologie, Univ. Mohammed V
Patrick Maurel: INSERM U1183, Institute of Regenerative Medicine and Biotherapy, University of Montpellier
Valérie Thiers: Institut Pasteur
Stéphane Bressanelli: Virologie Moléculaire et Structurale CNRS UPR 3296 - INRA UsC 1358
Didier Samuel: INSERM
Christian Bréchot: INSERM
Ama Gassama-Diagne: INSERM

Nature Communications, 2016, vol. 7, issue 1, 1-19

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12203

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