TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine.
TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine.
复制标题
DOI：
10.1083/jcb.202103105
复制
发表时间：
2021-06-07
期刊：
影响因子：
--
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Li YE;Wang Y;Du X;Zhang T;Mak HY;Hancock SE;McEwen H;Pandzic E;Whan RM;Aw YC;Lukmantara IE;Yuan Y;Dong X;Don A;Turner N;Qi S;Yang H
VMP1和TMEM41B是ER的膜蛋白，调节自噬体、脂滴和脂蛋白的形成。在这里，Li，Wang等人表明它们具有磷脂攀爬酶活性，这对于胆固醇和磷脂酰丝氨酸在哺乳动物细胞中的正常分布是必需的。TMEM41 B和VMP1是内质网（ER）的膜蛋白，调节自噬体、脂滴（LD）和脂蛋白的形成。最近，TMEM41 B被鉴定为所有冠状病毒和黄病毒感染的关键宿主因子。TMEM41 B和VMP1属于一个进化上保守的大家族，其分子功能仍然难以捉摸。在这里，我们表明，TMEM41 B和VMP1是磷脂的scramblases，其缺陷损害胆固醇和磷脂酰丝氨酸的正常细胞分布。它们对LD形成的作用机制可能与seipin不同。它们在维持细胞磷脂酰丝氨酸和胆固醇稳态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，细胞脂质的正确分选和分布是细胞器的生物合成和病毒感染所必需的。
VMP1 and TMEM41B, integral membrane proteins of the ER, regulate the formation of autophagosomes, lipid droplets, and lipoproteins. Here, Li, Wang, et al. show that they have phospholipid scramblase activity, which is essential to the normal distribution of cholesterol and phosphatidylserine in mammalian cells. 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.
登录
查看更多内容
影响因子：
13.6
作者：
Pomorski, Thomas Guenther;Menon, Anant K.
通讯作者：
Menon, Anant K.
影响因子：
4
作者：
Maekawa, Masashi;Fairn, Gregory D.
通讯作者：
Fairn, Gregory D.
影响因子：
64.5
作者：
Hoffmann HH;Schneider WM;Rozen-Gagnon K;Miles LA;Schuster F;Razooky B;Jacobson E;Wu X;Yi S;Rudin CM;MacDonald MR;McMullan LK;Poirier JT;Rice CM
通讯作者：
Rice CM
DOI：
10.1083/jcb.201311051
发表时间：
2014-03-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Pol A;Gross SP;Parton RG
通讯作者：
Parton RG
影响因子：
8.8
作者：
Pagac M;Cooper DE;Qi Y;Lukmantara IE;Mak HY;Wu Z;Tian Y;Liu Z;Lei M;Du X;Ferguson C;Kotevski D;Sadowski P;Chen W;Boroda S;Harris TE;Liu G;Parton RG;Huang X;Coleman RA;Yang H
通讯作者：
Yang H