受體介導的脂蛋白內質網輸出調控小鼠和人類的脂質穩態
作者：
小柯機器人發布時間：2020/11/16 13:55:27
北京大學陳曉偉研究組近日發現，受體介導的脂蛋白內質網輸出調控小鼠和人類的脂質穩態。相關論文於2020年11月12日在線發表在《細胞—代謝》雜誌上。
據研究人員介紹，在體內有效遞送特定貨物對分泌途徑構成了重大挑戰，該途徑將約30％的基因組編碼產物進行傳遞。新合成的蛋白質和脂質貨物通過COPII塗層囊泡由內質網（ER）上的GTPase SAR1組裝而進入分泌途徑，但是脂質運載脂蛋白如何與ER中的普通蛋白質貨物區分開並被選擇性分泌不清楚。
研究人員顯示此過程是由GTPase SAR1B和SURF4（高效貨物受體）定量控制的。雖然這兩個基因都與人類的脂質調節有關，但小鼠Sar1b或Surf4的肝失活會選擇性地將血漿脂質消耗至接近零，並保護小鼠免受動脈粥樣硬化的侵害。
這些發現表明，SURF4和SAR1B之間的配對可協同運行專門的、劑量敏感的循環脂質轉運程序，同時進一步暗示了治療動脈粥樣硬化和相關心臟代謝性疾病的轉化潛力。
附：英文原文
Title: Receptor-Mediated ER Export of Lipoproteins Controls Lipid Homeostasis in Mice and Humans
Author: Xiao Wang, Huimin Wang, Bolin Xu, Dong Huang, Chao Nie, Longjun Pu, Gregory J.M. Zajac, Han Yan, Jingru Zhao, Fangyuan Shi, Brian T. Emmer, Jia Lu, Rui Wang, Xiaohui Dong, Jianye Dai, Wenjing Zhou, Chu Wang, Ge Gao, Yan Wang, Cristen Willer, Xiangfeng Lu, Yuangang Zhu, Xiao-Wei Chen
Issue&Volume: 2020-11-12
Abstract: Efficient delivery of specific cargos in vivo poses a major challenge to the secretory pathway, which shuttles products encodedby ～30% of the genome. Newly synthesized protein and lipid cargos embark on the secretorypathway via COPII-coated vesicles, assembled by the GTPase SAR1 on the endoplasmicreticulum (ER), but how lipid-carrying lipoproteins are distinguished from the generalprotein cargos in the ER and selectively secreted has not been clear. Here, we showthat this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiencycargo receptor. While both genes are implicated in lipid regulation in humans, hepaticinactivation of either mouse Sar1b or Surf4 selectively depletes plasma lipids to near-zero and protects the mice from atherosclerosis.These findings show that the pairing between SURF4 and SAR1B synergistically operatesa specialized, dosage-sensitive transport program for circulating lipids, while furthersuggesting a potential translation to treat atherosclerosis and related cardio-metabolicdiseases.
DOI: 10.1016/j.cmet.2020.10.020
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30553-2