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

Author

Listed:
  • Abdellah Akil

    (INSERM
    University of Paris-Sud
    Laboratoire des Hépatites Virales
    Faculté des Sciences, Laboratoire de Biochimie-Immunologie, Univ. Mohammed V)

  • Juan Peng

    (INSERM
    University of Paris-Sud
    DHU Hepatinov)

  • Mohyeddine Omrane

    (INSERM
    University of Paris-Sud
    DHU Hepatinov)

  • Claire Gondeau

    (INSERM U1183, Institute of Regenerative Medicine and Biotherapy, University of Montpellier
    Department of Hepato-Gastroenterology A)

  • Christophe Desterke

    (University of Paris-Sud, -UFR medecine- INSERM UMS33)

  • Mickaël Marin

    (INSERM
    University of Paris-Sud)

  • Hélène Tronchère

    (INSERM U1048, I2MC and Université Paul Sabatier)

  • Cyntia Taveneau

    (Virologie Moléculaire et Structurale CNRS UPR 3296 - INRA UsC 1358)

  • Sokhavuth Sar

    (INSERM
    University of Paris-Sud)

  • Philippe Briolotti

    (INSERM U1183, Institute of Regenerative Medicine and Biotherapy, University of Montpellier
    Department of Hepato-Gastroenterology A)

  • Soumaya Benjelloun

    (Laboratoire des Hépatites Virales)

  • Abdelaziz Benjouad

    (Faculté des Sciences, Laboratoire de Biochimie-Immunologie, Univ. Mohammed V
    Univ. Internationale de Rabat)

  • Patrick Maurel

    (INSERM U1183, Institute of Regenerative Medicine and Biotherapy, University of Montpellier
    Department of Hepato-Gastroenterology A)

  • Valérie Thiers

    (Institut Pasteur)

  • Stéphane Bressanelli

    (Virologie Moléculaire et Structurale CNRS UPR 3296 - INRA UsC 1358)

  • Didier Samuel

    (INSERM
    University of Paris-Sud
    DHU Hepatinov
    AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire)

  • Christian Bréchot

    (INSERM
    University of Paris-Sud
    Institut Pasteur)

  • Ama Gassama-Diagne

    (INSERM
    University of Paris-Sud
    DHU Hepatinov)

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.

Suggested Citation

  • Abdellah Akil & Juan Peng & Mohyeddine Omrane & Claire Gondeau & Christophe Desterke & Mickaël Marin & Hélène Tronchère & Cyntia Taveneau & Sokhavuth Sar & Philippe Briolotti & Soumaya Benjelloun & Ab, 2016. "Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV," Nature Communications, Nature, vol. 7(1), pages 1-19, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12203
    DOI: 10.1038/ncomms12203
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