Control of Tobacco mosaic virus Movement Protein Fate by CELL-DIVISION-CYCLE Protein48
Control of Tobacco mosaic virus Movement Protein Fate by CELL-DIVISION-CYCLE Protein48
复制标题
DOI：
10.1104/pp.112.207399
复制
发表时间：
2012-12-01
期刊：
影响因子：
7.4
通讯作者：
Heinlein, Manfred
中科院分区：
文献类型：
--
作者：
Niehl, Annette;Amari, Khalid;Heinlein, Manfred
与许多其他病毒一样，烟草花叶病毒通过内质网（ER）进行复制，并利用这一膜网络通过胞间连丝（PD）进行细胞间传播，这一过程依赖于病毒编码的运动蛋白（MP）。运动过程包括MP与内质网和细胞骨架的相互作用以及其靶向PD。在感染周期的后期，MP进一步积累并定位于er相关的包涵体、病毒工厂和微管，然后最终被降解。尽管这些MP积累模式已被详细描述，但在感染期间控制MP命运和功能的潜在机制尚不清楚。在这里，我们鉴定了cell -分裂-周期蛋白48 (CDC48)，这是一种保守的伴侣蛋白，通过从膜或复合物中提取蛋白质底物来控制酵母（Saccharomyces cerevisiae）和动物细胞中的蛋白质命运，作为调节植物细胞中MP积累模式的细胞因子。我们证明了拟南芥（拟南芥）CDC48在感染后被诱导，与内质网包裹体中依赖于MP N端的MP相互作用，并促进蛋白质的降解。我们进一步提供证据表明，CDC48从内质网包裹体中提取MP到细胞质中，随后在微管上积累并稳定微管。我们发现，过表达CDC48会损害病毒的运动，这表明CDC48进一步通过从内质网转运途径中去除MP和促进MP对微管动力学的干扰来控制病毒的运动。CDC48也响应内质网中表达的其他蛋白，从而表明CDC48在内质网应激时对内质网膜维持的一般作用。
Like many other viruses, Tobacco mosaic virus replicates in association with the endoplasmic reticulum (ER) and exploits this membrane network for intercellular spread through plasmodesmata (PD), a process depending on virus-encoded movement protein (MP). The movement process involves interactions of MP with the ER and the cytoskeleton as well as its targeting to PD. Later in the infection cycle, the MP further accumulates and localizes to ER-associated inclusions, the viral factories, and along microtubules before it is finally degraded. Although these patterns of MP accumulation have been described in great detail, the underlying mechanisms that control MP fate and function during infection are not known. Here, we identify CELL-DIVISION-CYCLE protein48 (CDC48), a conserved chaperone controlling protein fate in yeast (Saccharomyces cerevisiae) and animal cells by extracting protein substrates from membranes or complexes, as a cellular factor regulating MP accumulation patterns in plant cells. We demonstrate that Arabidopsis (Arabidopsis thaliana) CDC48 is induced upon infection, interacts with MP in ER inclusions dependent on the MP N terminus, and promotes degradation of the protein. We further provide evidence that CDC48 extracts MP from ER inclusions to the cytosol, where it subsequently accumulates on and stabilizes microtubules. We show that virus movement is impaired upon overexpression of CDC48, suggesting that CDC48 further functions in controlling virus movement by removal of MP from the ER transport pathway and by promoting interference of MP with microtubule dynamics. CDC48 acts also in response to other proteins expressed in the ER, thus suggesting a general role of CDC48 in ER membrane maintenance upon ER stress.