Ferralli Jacqueline, Ashby Jamie, Fasler Monika, Boyko Vitaly, Heinlein Manfred
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
J Virol. 2006 Jun;80(12):5807-21. doi: 10.1128/JVI.00254-06.
The movement protein (MP) of Tobacco mosaic virus mediates the cell-to-cell transport of viral RNA through plasmodesmata, cytoplasmic cell wall channels for direct cell-to-cell communication between adjacent cells. Previous in vivo studies demonstrated that the RNA transport function of the protein correlates with its association with microtubules, although the exact role of microtubules in the movement process remains unknown. Since the binding of MP to microtubules is conserved in transfected mammalian cells, we took advantage of available mammalian cell biology reagents and tools to further address the interaction in flat-growing and transparent COS-7 cells. We demonstrate that neither actin, nor endoplasmic reticulum (ER), nor dynein motor complexes are involved in the apparent alignment of MP with microtubules. Together with results of in vitro coprecipitation experiments, these findings indicate that MP binds microtubules directly. Unlike microtubules associated with neuronal MAP2c, MP-associated microtubules are resistant to disruption by microtubule-disrupting agents or cold, suggesting that MP is a specialized microtubule binding protein that forms unusually stable complexes with microtubules. MP-associated microtubules accumulate ER membranes, which is consistent with a proposed role for MP in the recruitment of membranes in infected plant cells and may suggest that microtubules are involved in this process. The ability of MP to interfere with centrosomal gamma-tubulin is independent of microtubule association with MP, does not involve the removal of other tested centrosomal markers, and correlates with inhibition of centrosomal microtubule nucleation activity. These observations suggest that the function of MP in viral movement may involve interaction with the microtubule-nucleating machinery.
烟草花叶病毒的运动蛋白(MP)通过胞间连丝介导病毒RNA在细胞间的运输,胞间连丝是相邻细胞间直接进行细胞间通讯的细胞质细胞壁通道。先前的体内研究表明,该蛋白的RNA运输功能与其与微管的结合相关,尽管微管在运输过程中的确切作用仍不清楚。由于MP与微管的结合在转染的哺乳动物细胞中是保守的,我们利用现有的哺乳动物细胞生物学试剂和工具,在扁平生长且透明的COS-7细胞中进一步研究这种相互作用。我们证明,肌动蛋白、内质网(ER)或动力蛋白运动复合体均不参与MP与微管的明显排列。结合体外共沉淀实验结果,这些发现表明MP直接与微管结合。与与神经元MAP2c相关的微管不同,与MP相关的微管对微管破坏剂或低温破坏具有抗性,这表明MP是一种特殊的微管结合蛋白,能与微管形成异常稳定的复合体。与MP相关的微管会积累内质网膜,这与MP在受感染植物细胞中募集膜的假定作用一致,也可能表明微管参与了这一过程。MP干扰中心体γ-微管蛋白的能力独立于微管与MP的结合,不涉及去除其他测试的中心体标记物,且与中心体微管成核活性的抑制相关。这些观察结果表明,MP在病毒运动中的功能可能涉及与微管成核机制的相互作用。