School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, College of Life Sciences, Sichuan University, Chengdu, China.
J Cell Biol. 2021 Jun 7;220(6). doi: 10.1083/jcb.202103105.
TMEM41B and VMP1 are integral membrane proteins of the endoplasmic reticulum (ER) and regulate the formation of autophagosomes, lipid droplets (LDs), and lipoproteins. Recently, TMEM41B was identified as a crucial host factor for infection by all coronaviruses and flaviviruses. The molecular function of TMEM41B and VMP1, which belong to a large evolutionarily conserved family, remains elusive. Here, we show that TMEM41B and VMP1 are phospholipid scramblases whose deficiency impairs the normal cellular distribution of cholesterol and phosphatidylserine. Their mechanism of action on LD formation is likely to be different from that of seipin. Their role in maintaining cellular phosphatidylserine and cholesterol homeostasis may partially explain their requirement for viral infection. Our results suggest that the proper sorting and distribution of cellular lipids are essential for organelle biogenesis and viral infection.
TMEM41B 和 VMP1 是内质网（ER）的完整膜蛋白，可调节自噬体、脂滴（LD）和脂蛋白的形成。最近，TMEM41B 被鉴定为所有冠状病毒和黄病毒感染的关键宿主因子。TMEM41B 和 VMP1 属于一个大型进化保守家族，其分子功能仍然难以捉摸。在这里，我们表明 TMEM41B 和 VMP1 是磷脂翻转酶，其缺乏会损害胆固醇和磷脂酰丝氨酸的正常细胞分布。它们在 LD 形成中的作用机制可能与 seipin 不同。它们在维持细胞磷脂酰丝氨酸和胆固醇动态平衡中的作用可能部分解释了它们对病毒感染的需求。我们的研究结果表明，细胞脂质的正确分类和分布对于细胞器发生和病毒感染至关重要。
