A critical role of VMP1 in lipoprotein secretion
A critical role of VMP1 in lipoprotein secretion
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VMP1 在脂蛋白分泌中的关键作用
DOI：
10.7554/elife.48834
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发表时间：
2019-09-17
期刊：
影响因子：
7.7
通讯作者：
Mizushima, Noboru
中科院分区：
文献类型：
--
作者：
Morishita, Hideaki;Zhao, Yan G.;Mizushima, Noboru
脂蛋白是脂质-蛋白质复合物，主要由肠、肝脏和内脏内胚层产生和分泌，并输送到外周组织。在内质网 (ER) 膜中组装的脂蛋白被释放到 ER 腔中进行分泌，但其机制仍然很大程度上未知。在这里，我们证明脂蛋白从内质网膜上的释放需要VMP1，这是一种对于自噬和某些类型的分泌至关重要的内质网跨膜蛋白。斑马鱼中 vmp1 的缺失（而非其他自噬相关基因）会导致脂蛋白在肠道和肝脏中积聚。小鼠中Vmp1缺乏还会导致内脏内胚层和肠道中的脂质积累。在 VMP1 耗尽的细胞中，中性脂质积累在 ER 膜的脂质双层内，从而影响脂蛋白的分泌。这些结果表明，除了先前已知的功能外，VMP1 对于脂蛋白从 ER 膜到 ER 腔的释放也很重要。
Lipoproteins are lipid-protein complexes that are primarily generated and secreted from the intestine, liver, and visceral endoderm and delivered to peripheral tissues. Lipoproteins, which are assembled in the endoplasmic reticulum (ER) membrane, are released into the ER lumen for secretion, but its mechanism remains largely unknown. Here, we show that the release of lipoproteins from the ER membrane requires VMP1, an ER transmembrane protein essential for autophagy and certain types of secretion. Loss of vmp1, but not other autophagy-related genes, in zebrafish causes lipoprotein accumulation in the intestine and liver. Vmp1 deficiency in mice also leads to lipid accumulation in the visceral endoderm and intestine. In VMP1-depleted cells, neutral lipids accumulate within lipid bilayers of the ER membrane, thus affecting lipoprotein secretion. These results suggest that VMP1 is important for the release of lipoproteins from the ER membrane to the ER lumen in addition to its previously known functions.