Núcleo Tarcísio Pimenta de Pesquisa Genômica e Bioinformática, Universidade Estadual do Ceará, Fortaleza, CE Brazil.
Genet Mol Biol. 2009 Jul;32(3):652-65. doi: 10.1590/S1415-47572009000300033. Epub 2009 Sep 1.
Several motile processes are responsible for the movement of proteins into and within the flagellar membrane, but little is known about the process by which specific proteins (either actin-associated or not) are targeted to protozoan flagellar membranes. Actin is a major cytoskeleton protein, while polymerization and depolymerization of parasite actin and actin-interacting proteins (AIPs) during both processes of motility and host cell entry might be key events for successful infection. For a better understanding the eukaryotic flagellar dynamics, we have surveyed genomes, transcriptomes and proteomes of pathogenic Leishmania spp. to identify pertinent genes/proteins and to build in silico models to properly address their putative roles in trypanosomatid virulence. In a search for AIPs involved in flagellar activities, we applied computational biology and proteomic tools to infer from the biological meaning of coronins and Arp2/3, two important elements in phagosome formation after parasite phagocytosis by macrophages. Results presented here provide the first report of Leishmania coronin and Arp2/3 as flagellar proteins that also might be involved in phagosome formation through actin polymerization within the flagellar environment. This is an issue worthy of further in vitro examination that remains now as a direct, positive bioinformatics-derived inference to be presented.
几种运动过程负责将蛋白质运入和运出鞭毛膜，但对于特定蛋白质（无论是与肌动蛋白相关还是不相关）如何靶向原生动物鞭毛膜的过程知之甚少。肌动蛋白是一种主要的细胞骨架蛋白，而寄生虫肌动蛋白和肌动蛋白相互作用蛋白（AIP）的聚合和去聚合在运动和宿主细胞进入的两个过程中可能是成功感染的关键事件。为了更好地理解真核鞭毛动力学，我们调查了致病利什曼原虫属的基因组、转录组和蛋白质组，以鉴定相关基因/蛋白质，并构建计算机模型来正确解决它们在原生动物毒力中的假定作用。在寻找参与鞭毛活动的 AIP 时，我们应用计算生物学和蛋白质组学工具，从巨噬细胞吞噬寄生虫后吞噬体形成中的两个重要元件——冠状蛋白和 Arp2/3 的生物学意义中推断出来。这里提出的结果首次报道了利什曼原虫冠状蛋白和 Arp2/3 作为鞭毛蛋白，它们也可能通过鞭毛环境中的肌动蛋白聚合参与吞噬体的形成。这是一个值得进一步体外检查的问题，现在作为一个直接的、基于生物信息学的积极推断提出。
