Cideb, an ER- and Lipid Droplet-Associated Protein, Mediates VLDL Lipidation and Maturation by Interacting with Apolipoprotein B
Cideb, an ER- and Lipid Droplet-Associated Protein, Mediates VLDL Lipidation and Maturation by Interacting with Apolipoprotein B
复制标题
Cideb 是一种 ER 和脂滴相关蛋白，通过与载脂蛋白 B 相互作用介导 VLDL 脂化和成熟
DOI：
10.1016/j.cmet.2008.12.013
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发表时间：
2009-02-04
期刊：
影响因子：
29
通讯作者：
Li, Peng
中科院分区：
文献类型：
--
作者：
Ye, Jing;Li, John Zhong;Li, Peng
肝脏分泌富含三酰甘油的极低密度脂蛋白（VLDL）对于维持血浆脂质稳态至关重要。然而，VLDL 组装和脂化的过程尚未得到很好的表征。在这里，我们观察到 Cideb 缺失小鼠的肝脏三酰甘油水平较高，同时 VLDL 分泌水平较低。此外，Cideb 无效小鼠肝细胞分泌的 VLDL 颗粒具有低水平的三酰甘油，但 apoB 水平正常。我们还观察到 Cideb 定位于内质网和脂滴。重要的是，我们已经确定 apoB 是一种 Cideb 相互作用蛋白。通过将表达各种 Cideb 截短的腺病毒感染到 Cideb 缺失小鼠的肝细胞中，我们发现 Cideb 需要其 apoB 结合域和脂滴关联域来恢复富含三酰基甘油的 VLDL 颗粒的分泌。我们的数据表明，Cideb 促进富含三酰甘油的 VLDL 颗粒的形成，并提供对肝细胞中 VLDL 脂化和成熟的分子洞察。
Secretion of triacylglycerol-enriched very-low-density lipoproteins (VLDLs) from the liver is vital for maintaining plasma lipid homeostasis. However, the process of VLDL assembly and lipidation is not well characterized. Here, we observed that liver of Cideb null mice had higher levels of triacylglycerols accompanied by low level of VLDL secretion. Furthermore, VLDL particles secreted from hepatocytes of Cideb null mice have low levels of triacylglycerols but normal levels of apoB. We also observed that Cideb is localized to endoplasmic reticulum and lipid droplets. Importantly, we have identified apoB as a Cideb-inter-acting protein. By infecting adenoviruses expressing various Cideb truncations into hepatocytes of Cideb null mice, we found that Cideb requires both its apoB-binding and lipid droplet association domains to restore the secretion of triacyl glycerol-enriched VLDL particles. Our data suggest that Cideb promotes the formation of triacylglycerol-enriched VLDL particles and provides a molecular insight into VLDL lipidation and maturation in hepatocytes.