Primary cilia-dependent lipid raft/caveolin dynamics regulate adipogenesis

Cell Reports

卷:34

Kousuke Kasahara¹  Makoto Matsuyama²  Masaki Inagaki²  Yuhei Nishimura³  Yumi Maeno³  Daisuke Katoh⁴  Daishi Yamakawa⁴  Takashi Shiromizu⁴  Masatoshi Watanabe⁴  Chise Matsuda⁵ 

[1] Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan;

[2] Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan;

[3] Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan;

[4] Department of Physiology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan;

[5] Division of Molecular Genetics, Shigei Medical Research Institute, 2117 Yamada, Minami-ku, Okayama 701-0202, Japan;

关键词: primary cilia;    trichoplein;    adipogenesis;    insulin signaling;    lipid rafts;    caveolae;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Primary cilia play a pivotal role in signal transduction and development and are known to serve as signaling hubs. Recent studies have shown that primary cilium dysfunction influences adipogenesis, but the mechanisms are unclear. Here, we show that mesenchymal progenitors C3H10T1/2 depleted of trichoplein, a key regulator of cilium formation, have significantly longer cilia than control cells and fail to differentiate into adipocytes. Mechanistically, the elongated cilia prevent caveolin-1- and/or GM3-positive lipid rafts from being assembled around the ciliary base where insulin receptor proteins accumulate, thereby inhibiting the insulin-Akt signaling. We further generate trichoplein knockout mice, in which adipogenic progenitors display elongated cilia and impair the lipid raft dynamics. The knockout mice on an extended high-fat diet exhibit reduced body fat and smaller adipocytes than wild-type (WT) mice. Overall, our results suggest a role for primary cilia in regulating adipogenic signal transduction via control of the lipid raft dynamics around cilia.

【 授权许可】

Unknown