Mea6 controls VLDL transport through the coordinated regulation of COPII assembly
Mea6 controls VLDL transport through the coordinated regulation of COPII assembly
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Mea6 通过 COPII 组装的协调调节来控制 VLDL 运输
DOI：
10.1038/cr.2016.75
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发表时间：
2016-07-01
期刊：
影响因子：
44.1
通讯作者：
Xu, Zhiheng
中科院分区：
文献类型：
--
作者：
Wang, Yaqing;Liu, Liang;Xu, Zhiheng
脂肪堆积可能是由肝脏极低密度脂蛋白(VLDL)分泌紊乱引起的，可导致脂肪肝。极低密度脂蛋白是在内质网(ER)中合成的，并被运送到高尔基体分泌到血浆中。然而，极低密度脂蛋白转运的潜在分子机制仍然知之甚少。在这里，我们发现脑膜瘤表达抗原6(Mea6)/皮肤T细胞淋巴瘤相关抗原5C(CTAGE5C)的肝细胞特异性缺失会导致严重的脂肪肝和低脂血症。定量脂肪组学和蛋白质组学分析表明，Mea6/cTAGE5缺失会损害肝脏分泌不同类型的脂类和蛋白质，包括极低密度脂蛋白。此外，我们还证明了Mea6/cTAGE5与内质网外壳蛋白复合体II(COPII)的成分相互作用，当COPII耗尽时，也会导致肝细胞中的脂质积聚。我们的发现不仅揭示了调节脂质运输的几个新因素，而且也提供了证据，表明Mea6通过协调调节COPII机制在脂质运输中发挥关键作用。
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.