Small GTPase Rab40c associates with lipid droplets and modulates the biogenesis of lipid droplets.

Small GTPase Rab40c associates with lipid droplets and modulates the biogenesis of lipid droplets.
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小 GTP 酶 Rab40c 与脂滴结合并调节脂滴的生物发生

DOI:
10.1371/journal.pone.0063213
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Wang T
Wang T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tan R;Wang W;Wang S;Wang Z;Sun L;He W;Fan R;Zhou Y;Xu X;Hong W;Wang T

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小GTP酶Rab40c在哺乳动物细胞中的亚细胞定位和细胞生物学功能尚未得到详细研究。在这项研究中,我们证明外源表达的 GFP-Rab40c 与中性脂质特异性染料油红或尼罗红标记的脂滴相关,但不与高尔基体或内体标记相关。进一步检查表明,Rab40c 还与含有 ERGIC-53 的结构相关,尤其是在血清饥饿条件下。在 HepG2 细胞的脂滴形成和成熟过程中,Rab40c 越来越多地被招募到脂滴表面。 Rab40c 敲低会适度减小脂滴的大小,表明 Rab40c 参与脂滴的生物发生。刺激脂肪细胞分化会增加 3T3-L1 细胞中 Rab40c 的表达。 Rab40c 与 TIP47 相互作用,并与 TIP47 标记的脂滴并位相关。此外,Rab40c 的过度表达会导致脂滴聚集,与其 GTPase 活性无关,但完全依赖于 Rab40c 的完整 SOCS 盒结构域。此外,Rab40c 表现出自相互作用以及与 TIP47 的相互作用,SOCS 盒对于其诱导脂滴聚集的能力至关重要。我们的结果表明 Rab40c 是一种与脂滴相关的新型 Rab 蛋白,并且可能参与调节脂滴的生物发生。
The subcellular location and cell biological function of small GTPase Rab40c in mammalian cells have not been investigated in detail. In this study, we demonstrated that the exogenously expressed GFP-Rab40c associates with lipid droplets marked by neutral lipid specific dye Oil red or Nile red, but not with the Golgi or endosomal markers. Further examination demonstrated that Rab40c is also associated with ERGIC-53 containing structures, especially under the serum starvation condition. Rab40c is increasingly recruited to the surface of lipid droplets during lipid droplets formation and maturation in HepG2 cells. Rab40c knockdown moderately decreases the size of lipid droplets, suggesting that Rab40c is involved in the biogenesis of lipid droplets. Stimulation for adipocyte differentiation increases the expression of Rab40c in 3T3-L1 cells. Rab40c interacts with TIP47, and is appositionally associated with TIP47-labeled lipid droplets. In addition, over-expression of Rab40c causes the clustering of lipid droplets independent of its GTPase activity, but completely dependent of the intact SOCS box domain of Rab40c. In addition, Rab40c displayed self-interaction as well as interaction with TIP47 and the SOCS box is essential for its ability to induce clustering of lipid droplets. Our results suggest that Rab40c is a novel Rab protein associated with lipid droplets, and is likely involved in modulating the biogenesis of lipid droplets.
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