TY - JOUR
T1 - Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV
AU - Akil, Abdellah
AU - Peng, Juan
AU - Omrane, Mohyeddine
AU - Gondeau, Claire
AU - Desterke, Christophe
AU - Marin, Mickaël
AU - Tronchère, Hélène
AU - Taveneau, Cyntia
AU - Sar, Sokhavuth
AU - Briolotti, Philippe
AU - Benjelloun, Soumaya
AU - Benjouad, Abdelaziz
AU - Maurel, Patrick
AU - Thiers, Valérie
AU - Bressanelli, Stéphane
AU - Samuel, Didier
AU - Bréchot, Christian
AU - Gassama-Diagne, Ama
PY - 2016/7/15
Y1 - 2016/7/15
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms12203
DO - 10.1038/ncomms12203
M3 - Article
C2 - 27417143
AN - SCOPUS:84978764257
SN - 2041-1723
VL - 7
JO - Nature communications
JF - Nature communications
M1 - 12203
ER -