Mea6 controls VLDL transport through the coordinated regulation of COPII assembly

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2016

Erschienen:

2016

Enthalten in:

Zur Gesamtaufnahme - volume:26

Enthalten in:

Cell research - 26(2016), 7 vom: 25. Juli, Seite 787-804

Sprache:

Englisch

Beteiligte Personen:

Wang, Yaqing [VerfasserIn]
Liu, Liang [VerfasserIn]
Zhang, Hongsheng [VerfasserIn]
Fan, Junwan [VerfasserIn]
Zhang, Feng [VerfasserIn]
Yu, Mei [VerfasserIn]
Shi, Lei [VerfasserIn]
Yang, Lin [VerfasserIn]
Lam, Sin Man [VerfasserIn]
Wang, Huimin [VerfasserIn]
Chen, Xiaowei [VerfasserIn]
Wang, Yingchun [VerfasserIn]
Gao, Fei [VerfasserIn]
Shui, Guanghou [VerfasserIn]
Xu, Zhiheng [VerfasserIn]

Links:

Volltext

Themen:

Antigens, Neoplasm
Apolipoproteins B
Apolipoproteins E
Journal Article
Lipoproteins, VLDL
MIA2 protein, human
Neoplasm Proteins
Protein Subunits
Proteome
Vesicular Transport Proteins

Anmerkungen:

Date Completed 28.12.2017

Date Revised 14.12.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1038/cr.2016.75

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM261469231