DFCP1 associates with lipid droplets
DFCP1 associates with lipid droplets
复制标题
DFCP1 与脂滴相关
DOI：
10.1002/cbin.11199
复制
发表时间：
2019-07-23
影响因子：
3.9
通讯作者：
Xu, Li
中科院分区：
文献类型：
--
作者：
Gao, Guangang;Sheng, Yuanyuan;Xu, Li
双FYVE-containing protein 1 （DFCP1）普遍表达，通过与磷脂酰肌醇-3-磷酸（PI3P）的特异性相互作用参与细胞膜内运输和标记大粒体。先前的研究表明，亚细胞DFCP1蛋白显示多细胞器定位，包括内质网（ER）、高尔基体和线粒体。然而，其在脂滴（ld）上的定位和功能尚不清楚。在这里，我们证明了DFCP1在油酸孵育后定位在LD上。DFCP1的er靶向结构域对于其LD定位是必不可少的，双FYVE结构域进一步增强了这一功能。通过wortmannin处理或C654S和C770S双突变抑制PI3P在FYVE结构域的结合对DFCP1的LD定位没有影响。这表明DFCP1靶向大体和ld的机制是不同的。MEF细胞缺乏DFCP1导致LD数量增加，LD大小减小。有趣的是，DFCP1与gtp结合的Rab18（一种ld相关蛋白）相互作用。综上所述，我们的研究表明DFCP1的动态定位受到营养状况的调节，以响应细胞代谢。
Double FYVE-containing protein 1 (DFCP1) is ubiquitously expressed, participates in intracellular membrane trafficking and labels omegasomes through specific interactions with phosphatidylinositol-3-phosphate (PI3P). Previous studies showed that subcellular DFCP1 proteins display multi-organelle localization, including in the endoplasmic reticulum (ER), Golgi apparatus and mitochondria. However, its localization and function on lipid droplets (LDs) remain unclear. Here, we demonstrate that DFCP1 localizes to the LD upon oleic acid incubation. The ER-targeted domain of DFCP1 is indispensable for its LD localization, which is further enhanced by double FYVE domains. Inhibition of PI3P binding at the FYVE domain through wortmannin treatment or double mutation at C654S and C770S have no effect on DFCP1's LD localization. These show that the mechanisms for DFCP1 targeting the omegasome and LDs are different. DFCP1 deficiency in MEF cells causes an increase in LD number and reduces LD size. Interestingly, DFCP1 interacts with GTP-bound Rab18, an LD-associated protein. Taken together, our work demonstrates the dynamic localization of DFCP1 is regulated by nutritional status in response to cellular metabolism.