Proteomic analysis of mitochondrial-associated ER membranes (MAM) during RNA virus infection reveals dynamic changes in protein and organelle trafficking.
Proteomic analysis of mitochondrial-associated ER membranes (MAM) during RNA virus infection reveals dynamic changes in protein and organelle trafficking.
复制标题
DOI：
10.1371/journal.pone.0117963
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Gale M Jr
中科院分区：
文献类型：
--
作者：
Horner SM;Wilkins C;Badil S;Iskarpatyoti J;Gale M Jr
针对RNA病毒感染的先天免疫的RIG-I途径信号传导在ER和线粒体之间组织在称为线粒体相关ER膜（MAM）的ER亚结构域上。RIG-I衔接蛋白MAVS传递抗病毒免疫的下游信号，信号复合物与线粒体和过氧化物酶体一起组装在MAM上。为了确定组件，调节MAVS信号体组装的MAM，我们的特点是MAM，ER，和细胞质的蛋白质组感染慢性（丙型肝炎）或急性（仙台）RNA病毒感染的细胞，以及模拟感染的细胞。慢性和急性病毒感染期间蛋白质运输动力学的比较分析揭示了RIG-I途径激活期间MAM中的差异蛋白质谱。我们确定了在慢性和急性RNA病毒感染中招募进入和离开MAM的蛋白质和生化途径，代表了驱动免疫和/或调节病毒复制的蛋白质。此外，通过使用这种比较蛋白质组学方法，我们确定了3个新的MAVS相互作用蛋白，RAB 1B，VTN和LONP 1，并将LONP 1定义为RIG-I途径的正调节因子。我们的蛋白质组学分析还揭示了在急性和慢性RNA病毒感染期间亚细胞区室之间的动态串扰，并证明了MAM作为协调先天免疫信号传导以启动针对RNA病毒感染的免疫的中心平台的重要性。
RIG-I pathway signaling of innate immunity against RNA virus infection is organized between the ER and mitochondria on a subdomain of the ER called the mitochondrial-associated ER membrane (MAM). The RIG-I adaptor protein MAVS transmits downstream signaling of antiviral immunity, with signaling complexes assembling on the MAM in association with mitochondria and peroxisomes. To identify components that regulate MAVS signalosome assembly on the MAM, we characterized the proteome of MAM, ER, and cytosol from cells infected with either chronic (hepatitis C) or acute (Sendai) RNA virus infections, as well as mock-infected cells. Comparative analysis of protein trafficking dynamics during both chronic and acute viral infection reveals differential protein profiles in the MAM during RIG-I pathway activation. We identified proteins and biochemical pathways recruited into and out of the MAM in both chronic and acute RNA viral infections, representing proteins that drive immunity and/or regulate viral replication. In addition, by using this comparative proteomics approach, we identified 3 new MAVS-interacting proteins, RAB1B, VTN, and LONP1, and defined LONP1 as a positive regulator of the RIG-I pathway. Our proteomic analysis also reveals a dynamic cross-talk between subcellular compartments during both acute and chronic RNA virus infection, and demonstrates the importance of the MAM as a central platform that coordinates innate immune signaling to initiate immunity against RNA virus infection.
登录
查看更多内容
影响因子：
6.7
作者：
Arnaud N;Dabo S;Akazawa D;Fukasawa M;Shinkai-Ouchi F;Hugon J;Wakita T;Meurs EF
通讯作者：
Meurs EF
DOI：
10.1126/science.1189157
发表时间：
2010-11-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Giorgi C;Ito K;Lin HK;Santangelo C;Wieckowski MR;Lebiedzinska M;Bononi A;Bonora M;Duszynski J;Bernardi R;Rizzuto R;Tacchetti C;Pinton P;Pandolfi PP
通讯作者：
Pandolfi PP
影响因子：
64.5
作者：
Dixit E;Boulant S;Zhang Y;Lee AS;Odendall C;Shum B;Hacohen N;Chen ZJ;Whelan SP;Fransen M;Nibert ML;Superti-Furga G;Kagan JC
通讯作者：
Kagan JC
影响因子：
11.4
作者：
Csordás, G;Thomas, AP;Hajnóczky, G
通讯作者：
Hajnóczky, G
影响因子：
5.5
作者：
Hajnóczky, G;Csordás, G;Pacher, P
通讯作者：
Pacher, P