Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility.
Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility.
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DOI：
10.1074/jbc.m117.802769
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发表时间：
2017-10-27
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Holder AA
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作者：
Green JL;Wall RJ;Vahokoski J;Yusuf NA;Ridzuan MAM;Stanway RR;Stock J;Knuepfer E;Brady D;Martin SR;Howell SA;Pires IP;Moon RW;Molloy JE;Kursula I;Tewari R;Holder AA
肌球蛋白A（MyoA）是一种XIV类肌球蛋白，与疟疾寄生虫的滑行运动和宿主细胞和组织入侵有关。MyoA是称为滑体的膜相关蛋白复合物的一部分，滑体是寄生虫运动所必需的，包括MyoA轻链肌球蛋白尾结构域相互作用蛋白（MTIP）和几种滑体相关蛋白（GAP）。然而，大多数关于MyoA的研究都集中在寄生虫生命周期的单个阶段。我们研究了MyoA在哺乳动物和昆虫宿主中伯氏疟原虫整个生命周期的表达。在细胞外动合子、子孢子和裂殖子中，MyoA位于寄生虫的外周。在有性阶段，受精卵形成和初始的动合子分化之前MyoA的合成和沉积，这只发生在发展中的突起。在发展中的细胞内无性血液阶段，MyoA在成熟的裂殖子中合成，并位于分裂的裂殖子的外围，在那里它保持整个成熟，裂殖子出口和宿主细胞入侵。除了疟原虫中已知的GAP外，该复合物还包括GAP 40，一种称为必需轻链（ELC）的额外肌球蛋白轻链和几种其他候选组分。该ELC结合邻近MTIP结合位点的MyoA颈部区域，并且两条肌球蛋白轻链共同定位于滑粒。MyoA与其两条轻链的共表达揭示了两条轻链的存在增强了MyoA依赖的肌动蛋白运动性。总之，我们已经建立了一个系统来研究这三种滑体成分的相互作用和功能，从而能够评估靶向该运动复合物以阻断宿主细胞侵袭的抑制剂。
Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain myosin tail domain–interacting protein (MTIP) and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites, and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress, and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC), and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP-binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion.