Primary cilium suppression by SREBP1c involves distortion of vesicular trafficking by PLA2G3

被引：16

作者：

Gijs, Hannah Laura ^{[1
]}

Willemarck, Nicolas ^{[1
]}

Vanderhoydonc, Frank ^{[1
]}

Khan, Niamat Ali ^{[1
]}

Dehairs, Jonas ^{[1
]}

Derua, Rita

Waelkens, Etienne

Taketomi, Yoshitaka ^{[6
]}

Murakami, Makoto ^{[6
,7
]}

Agostinis, Patrizia ^{[2
,3
]}

Annaert, Wim ^{[4
,5
]}

Swinnen, Johannes V. ^{[1
]}

机构：

[1] Univ Leuven, KU Leuven, Dept Oncol, Lab Lipid Metab & Canc, B-3000 Louvain, Belgium

[2] Univ Leuven, Lab Prot Phosphorylat & Prote, KU Leuven, B-3000 Louvain, Belgium

[3] Univ Leuven, Lab Cell Death Res & Therapy, Dept Cellular & Mol Med, KU Leuven, B-3000 Louvain, Belgium

[4] Univ Leuven, Lab Membrane Trafficking, Ctr Biol Dis, KU Leuven, B-3000 Louvain, Belgium

[5] Univ Leuven, Dept Human Genet, KU Leuven, B-3000 Louvain, Belgium

[6] Tokyo Metropolitan Inst Med Sci, Lipid Metab Project, Dept Adv Sci Biomol, Tokyo 1568506, Japan

[7] Japan Sci & Technol Agcy, CREST, Saitama 3320012, Japan

来源：

MOLECULAR BIOLOGY OF THE CELL | 2015年 / 26卷 / 12期

基金：

日本科学技术振兴机构;

关键词：

STEROL REGULATORY ELEMENT; FATTY-ACID SYNTHASE; SECRETED PHOSPHOLIPASES A(2); GROUP-III; CANCER; PROTEIN; EXPRESSION; CILIOGENESIS; CHOLESTEROL; ACTIVATION;

D O I：

10.1091/mbc.E14-10-1472

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Distortion of primary cilium formation is increasingly recognized as a key event in many human pathologies. One of the underlying mechanisms involves aberrant activation of the lipogenic transcription factor sterol regulatory element-binding protein 1c (SREBP1c), as observed in cancer cells. To gain more insight into the molecular pathways by which SREBP1c suppresses primary ciliogenesis, we searched for overlap between known ciliogenesis regulators and targets of SREBP1. One of the candidate genes that was consistently up-regulated in cellular models of SREBP1c-induced cilium repression was phospholipase A2 group III (PLA2G3), a phospholipase that hydrolyzes the sn-2 position of glycerophospholipids. Use of RNA interference and a chemical inhibitor of PLA2G3 rescued SREBP1c-induced cilium repression. Cilium repression by SREBP1c and PLA2G3 involved alterations in endosomal recycling and vesicular transport toward the cilium, as revealed by aberrant transferrin and Rab11 localization, and was largely mediated by an increase in lysophosphatidylcholine and lysophosphatidylethanolamine levels. Together these findings indicate that aberrant activation of SREBP1c suppresses primary ciliogenesis by PLA2G3-mediated distortion of vesicular trafficking and suggest that PLA2G3 is a novel potential target to normalize ciliogenesis in SREBP1c-overexpressing cells, including cancer cells.

引用

页码：2321 / 2332

页数：12