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

被引：57

作者：

Akil, Abdellah ^{[1
,2
,3
,4
]}

Peng, Juan ^{[1
,2
,5
]}

Omrane, Mohyeddine ^{[1
,2
,5
]}

Gondeau, Claire ^{[6
,7
]}

Desterke, Christophe ^{[8
]}

Marin, Mickael ^{[1
,2
]}

Tronchere, Helene ^{[9
,10
]}

Taveneau, Cyntia ^{[11
]}

Sar, Sokhavuth ^{[1
,2
]}

Briolotti, Philippe ^{[6
,7
]}

Benjelloun, Soumaya ^{[3
]}

Benjouad, Abdelaziz ^{[4
,12
]}

Maurel, Patrick ^{[6
,7
]}

Thiers, Valerie

Bressanelli, Stphane ^{[11
]}

Samuel, Didier ^{[1
,2
,5
,14
]}

Brechot, Christian ^{[1
,2
,13
]}

Gassama-Diagne, Ama ^{[1
,2
,5
]}

机构：

[1] INSERM, U1193, F-94800 Villejuif, France

[2] Univ Paris Sud, UMR S 1193, F-94800 Villejuif, France

[3] Inst Pasteur Maroc, Dept Virol, Lab Hepatites Virales, BP 20360, Casablanca, Morocco

[4] Univ Mohammed 5, Fac Sci, Lab Biochim Immunol, Rabat, Morocco

[5] DHU Hepatinov, F-94800 Villejuif, France

[6] Univ Montpellier, INSERM, U1183, Inst Regenerat Med & Biotherapy, F-34295 Montpellier, France

[7] CHRU, Dept Hepatogastroenterol A, Hosp St Eloi, F-34295 Montpellier, France

[8] Univ Paris Sud, UFR Med, INSERM, UMS33, Villejuif, France

[9] INSERM, U1048, I2MC, F-31432 Toulouse, France

[10] Univ Toulouse 3, F-31432 Toulouse, France

[11] CNRS, UPR 3296, INRA UsC 1358, Virol Mol & Struct, F-91198 Gif Sur Yvette, France

[12] Univ Int Rabat, Sala Al Jadida, Morocco

[13] Inst Pasteur, F-75724 Paris, France

[14] Hop Paul Brousse, AP HP, Ctr Hepatobiliaire, F-94800 Villejuif, France

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

关键词：

HEPATITIS-C VIRUS; CORE PROTEIN; YEAST SEPTIN; CELL; PHOSPHOINOSITIDES; MEMBRANE; PTDINS5P; LOCALIZATION; CYTOSKELETON; REPLICATION;

D O I：

10.1038/ncomms12203

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：19

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