Li Hongqiang, Chen Ao, Shu Le, Yu Xiaolan, Gan Li, Zhou Lei, Yang Zaiqing
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
Genes Cells. 2014 Nov;19(11):793-802. doi: 10.1111/gtc.12180. Epub 2014 Sep 25.
The CIDEC protein is located in lipid droplets (LDs) and the endoplasmic reticulum (ER) and is induced in fat deposition. However, the binding domain, the functional domain and the underlying mechanism of CIDEC in stimulating lipid accumulation remain unclear. Here, we investigated the subcellular localization and function of pig CIDEC and confirmed CIDEC promotes unilocular development of LDs, reduces the specific surface area (SSA) of LDs and stimulates lipid accumulation in HepG2 cells. By analyzing a series of CIDEC mutants, we showed the N-domain (1-173 amino acid) is involved in LD localization and the C-domain (174-238 amino acid) is necessary for LD fusion. Further analysis indicated that the 106-173 amino acid region includes an ER-binding domain. Moreover, CIDEC stayed in the ER under lipid-deficient conditions and translocated to LDs under fatty acid stimulation suggesting that localization of CIDEC in the ER is before the LD. Our data indicated additional fatty acids stimulated hepatic CIDEC expression and an increasing level of CIDEC induced hepatic LD fusion and lipid accumulation. Our work suggests that CIDEC protects LDs by decreasing the SSA of LDs and is involved in the regulation of hepatic lipid deposition.
CIDEC蛋白位于脂滴（LDs）和内质网（ER）中，在脂肪沉积过程中被诱导表达。然而，CIDEC在刺激脂质积累中的结合结构域、功能结构域及潜在机制仍不清楚。在此，我们研究了猪CIDEC的亚细胞定位和功能，并证实CIDEC促进脂滴的单室发育，降低脂滴的比表面积（SSA），并刺激HepG2细胞中的脂质积累。通过分析一系列CIDEC突变体，我们发现N结构域（第1 - 173个氨基酸）参与脂滴定位，C结构域（第174 - 238个氨基酸）是脂滴融合所必需的。进一步分析表明，第106 - 173个氨基酸区域包含一个内质网结合结构域。此外，在脂质缺乏条件下，CIDEC停留在内质网中，而在脂肪酸刺激下转移到脂滴，这表明CIDEC在内质网中的定位先于脂滴。我们的数据表明，额外的脂肪酸刺激肝脏CIDEC表达，而CIDEC水平的升高诱导肝脏脂滴融合和脂质积累。我们的研究表明，CIDEC通过降低脂滴的比表面积来保护脂滴，并参与肝脏脂质沉积的调节。
