期刊
EMBO JOURNAL
卷 38, 期 8, 页码 -出版社
WILEY
DOI: 10.15252/embj.2018100156
关键词
Cideb; COPII vesicles; fatty liver; lipid metabolism; SREBP
资金
- National Key R&D Program of China [2016YFA0502002]
- National Natural Science Foundation of China [31430040, 31690103, 31621063, 31571213, 31521062]
- Young 1000 Talent Plan
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.
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