Volume 26, No 7, Jul 2016

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 26 Issue 7, July 2016: 787-804

ORIGINAL ARTICLES

Mea6 controls VLDL transport through the coordinated regulation of COPII assembly

Yaqing Wang^1,*, Liang Liu^1,2,*, Hongsheng Zhang^1,2, Junwan Fan^1,2, Feng Zhang^1,2, Mei Yu³, Lei Shi¹, Lin Yang¹, Sin Man Lam¹, Huimin Wang⁴, Xiaowei Chen⁴, Yingchun Wang¹, Fei Gao⁵, Guanghou Shui¹ and Zhiheng Xu^1,6

¹State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
²University of Chinese Academy of Sciences, Beijing 100101, China
³School of Life Science, Shandong University, Jinan 250100, China
⁴Institute of Molecular Medicine, Peking University, Beijing 100871, China
⁵State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
⁶Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China Correspondence: Zhiheng Xu, E-mail: zhxu@genetics.ac.cn; Yaqing Wang,(yaqingwang@genetics.ac.cn)

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.

10.1038/cr.2016.75

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