Baum Jake, Tonkin Christopher J, Paul Aditya S, Rug Melanie, Smith Brian J, Gould Sven B, Richard Dave, Pollard Thomas D, Cowman Alan F
Infection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Cell Host Microbe. 2008 Mar 13;3(3):188-98. doi: 10.1016/j.chom.2008.02.006.
Malaria parasites invade host cells using actin-based motility, a process requiring parasite actin filament nucleation and polymerization. Malaria and other apicomplexan parasites lack Arp2/3 complex, an actin nucleator widely conserved across eukaryotes, but do express formins, another type of actin nucleator. Here, we demonstrate that one of two malaria parasite formins, Plasmodium falciparum formin 1 (PfFormin 1), and its ortholog in the related parasite Toxoplasma gondii, follows the moving tight junction between the invading parasite and the host cell, which is the predicted site of the actomyosin motor that powers motility. Furthermore, in vitro, the PfFormin1 actin-binding formin homology 2 domain is a potent nucleator, stimulating actin polymerization and, like other formins, localizing to the barbed end during filament elongation. These findings support a conserved molecular mechanism underlying apicomplexan parasite motility and, given the essential role that actin plays in cell invasion, highlight formins as important determinants of malaria parasite pathogenicity.
疟原虫利用基于肌动蛋白的运动性侵入宿主细胞，这一过程需要寄生虫肌动蛋白丝的成核和聚合。疟疾和其他顶复门寄生虫缺乏Arp2/3复合物（一种在真核生物中广泛保守的肌动蛋白成核因子），但确实表达formin（另一种肌动蛋白成核因子）。在此，我们证明疟原虫的两种formin之一，恶性疟原虫formin 1（PfFormin 1）及其在相关寄生虫刚地弓形虫中的直系同源物，会跟随入侵寄生虫与宿主细胞之间移动的紧密连接，而紧密连接是驱动运动性的肌动球蛋白马达的预测位点。此外，在体外，PfFormin1的肌动蛋白结合formin同源2结构域是一种强大的成核因子，可刺激肌动蛋白聚合，并且与其他formin一样，在丝伸长过程中定位于带刺末端。这些发现支持了顶复门寄生虫运动性背后的保守分子机制，并且鉴于肌动蛋白在细胞入侵中起的关键作用，突出了formin作为疟原虫致病性的重要决定因素。
