标题：Mea6 controls VLDL transport through the coordinated regulation of COPII assembly
作者：Wang, Yaqing; Liu, Liang; Zhang, Hongsheng; Fan, Junwan; Zhang, Feng; Yu, Mei; Shi, Lei; Yang, Lin; Lam, Sin Man; Wang, Huimin; Ch 更多 作者机构：[Wang Yaqing] Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, State Key Laboratory of Molecular Developmental Biology, B 更多
通讯作者地址：[Wang, YQ; Xu, ZH]Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China;[Xu, ZH]Tongji Univ, Sch Med, T 更多
关键词：Mea6; fatty liver; lipid transport and VLDL secretion; COPII machinery
摘要：Lipid accumulation, which may be caused by the disturbance in very low density lipoprotein (VLDL) secretion in the liver, can lead to fatty liver disease. VLDL is synthesized in endoplasmic reticulum (ER) and transported to Golgi apparatus for secretion into plasma. However, the underlying molecular mechanism for VLDL transport is still poorly understood. Here we show that hepatocyte-specific deletion of meningioma-expressed antigen 6 (Mea6)/cutaneous T cell lymphoma-associated antigen 5C (cTAGE5C) leads to severe fatty liver and hypolipemia in mice. Quantitative lipidomic and proteomic analyses indicate that Mea6/cTAGE5 deletion impairs the secretion of different types of lipids and proteins, including VLDL, from the liver. Moreover, we demonstrate that Mea6/cTAGE5 interacts with components of the ER coat protein complex II (COPII) which, when depleted, also cause lipid accumulation in hepatocytes. Our findings not only reveal several novel factors that regulate lipid transport, but also provide evidence that Mea6 plays a critical role in lipid transportation through the coordinated regulation of the COPII machinery.