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

Nat Commun. 2016 Jul 15;7:12203. doi: 10.1038/ncomms12203.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Regulation
  • Hepacivirus / pathogenicity*
  • Hepacivirus / physiology
  • Hepatitis C / metabolism
  • Host-Pathogen Interactions / physiology
  • Humans
  • Lipid Droplets / drug effects
  • Lipid Droplets / metabolism*
  • Lipid Metabolism / physiology
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / virology
  • Microtubules / metabolism*
  • Microtubules / virology
  • Oleic Acid / pharmacology
  • Phosphatidylinositol Phosphates / metabolism*
  • Septins / genetics
  • Septins / metabolism*
  • Virus Replication

Substances

  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 5-phosphate
  • Oleic Acid
  • osteum
  • SEPTIN9 protein, human
  • Septins