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Cideb controls sterol‐regulated ER export of SREBP / SCAP by promoting cargo loading at ER exit sites
Author(s) -
Su Lu,
Zhou Linkang,
Chen FengJung,
Wang Huimin,
Qian Hui,
Sheng Yuanyuan,
Zhu Yuangang,
Yu Hua,
Gong Xinqi,
Cai Li'e,
Yang Xuerui,
Xu Li,
Zhao TongJin,
Li John Zhong,
Chen XiaoWei,
Li Peng
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018100156
Subject(s) - sterol regulatory element binding protein , biology , sterol , biochemistry , cholesterol
SREBP s 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.