| Title | Cideb controls sterol-regulated ER export of SREBP/SCAP by promoting cargo loading at ER exit sites |
| Authors | Su, Lu Zhou, Linkang Chen, Feng-Jung Wang, Huimin Qian, Hui Sheng, Yuanyuan Zhu, Yuangang Yu, Hua Gong, Xinqi Cai, Li'e Yang, Xuerui Xu, Li Zhao, Tong-Jin Li, John Zhong Chen, Xiao-Wei Li, Peng |
| Affiliation | Tsinghua Univ, State Key Lab Membrane Biol, Sch Life Sci, Beijing, Peoples R China Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Sch Life Sci, Beijing, Peoples R China Peking Univ, Inst Mol Med, Ctr Life Sci, State Key Lab Membrane Biol, Beijing, Peoples R China Zhejiang Univ, Affiliated Hosp 1, Hangzhou, Zhejiang, Peoples R China Zhejiang Univ, Ctr Stem Cell & Regenerat Med, Dept Basic Med Sci, Sch Med,Inst Hematol, Hangzhou, Zhejiang, Peoples R China Renmin Univ China, Inst Math Sci, Math Intelligence Applicat Lab, Beijing, Peoples R China Nanjing Med Univ, Key Lab Human Funct Genom Jiangsu Prov, Key Lab Rare Metab Dis, Nanjing, Jiangsu, Peoples R China Nanjing Med Univ, Dept Mol Biol & Biochem, Nanjing, Jiangsu, Peoples R China Tsinghua Univ, Sch Life Sci, Ctr Synthet & Syst Biol, MOE Key Lab Bioinformat, Beijing, Peoples R China Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen, Fujian, Peoples R China |
| Keywords | Cideb COPII vesicles fatty liver lipid metabolism SREBP |
| Issue Date | 2019 |
| Publisher | EMBO JOURNAL |
| Abstract | SREBPs are master regulators of lipid homeostasis and undergo sterol-regulated export from ER to Golgi apparatus for processing and activation via COPII-coated vesicles. While COPII recognizes SREBP through its escort protein SCAP, factor(s) specifically promoting SREBP/SCAP loading to the COPII machinery remains unknown. Here, we show that the ER/lipid droplet-associated protein Cideb selectively promotes the loading of SREBP/SCAP into COPII vesicles. Sterol deprivation releases SCAP from Insig and enhances ER export of SREBP/SCAP by inducing SCAP-Cideb interaction, thereby modulating sterol sensitivity. Moreover, Cideb binds to the guanine nucleotide exchange factor Sec12 to enrich SCAP/SREBP at ER exit sites, where assembling of COPII complex initiates. Loss of Cideb inhibits the cargo loading of SREBP/SCAP, reduces SREBP activation, and alleviates diet-induced hepatic steatosis. Our data point to a linchpin role of Cideb in regulated ER export of SREBP and lipid homeostasis. |
| URI | http://hdl.handle.net/20.500.11897/549070 |
| ISSN | 0261-4189 |
| DOI | 10.15252/embj.2018100156 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 分子医学研究所 膜生物学国家重点实验室 |
