A circular zone of attachment to the extracellular matrix provides directionality to the motility of Toxoplasma gondii in 3D.
A circular zone of attachment to the extracellular matrix provides directionality to the motility of Toxoplasma gondii in 3D.
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DOI：
10.7554/elife.85171
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发表时间：
2022-12-15
期刊：
影响因子：
7.7
通讯作者：
Ward GE
中科院分区：
文献类型：
--
作者：
Stadler RV;Nelson SR;Warshaw DM;Ward GE
弓形虫是一种原生动物寄生虫，感染世界上 30-40% 的人口。感染通常是亚临床的，但可能很严重，在某些情况下甚至危及生命。弓形虫毒力的核心是一种不寻常的底物依赖性运动，这种运动使寄生虫能够侵入宿主细胞并在全身传播。具有运动功能的蛋白质异寡聚复合物已被表征，但这些蛋白质如何共同作用以驱动寄生虫向前运动仍然存在争议。了解潜在机制所需的关键信息是移动寄生虫对外部环境施加的力的方向性。运动的线性运动模型在过去二十年中占据了该领域的主导地位，它预测沿着寄生虫的长度会产生连续的前后力。我们在这里使用三维牵引力映射显示，移动寄生虫施加的主要力是周期性的，并且在细胞外基质内的固定圆形位置指向寄生虫。这些高度局部化的力是由寄生虫拉动基质产生的，在寄生虫的质膜中产生明显的收缩。我们提出，向内力的环对应于寄生虫和基质之间的圆周附着区域，寄生虫通过该附着区域推动自身向前移动。综合数据表明，寄生虫运动和宿主细胞入侵的机制之间的联系比以前认识的更紧密。在缺乏主要表面粘附素 TgMIC2 的寄生虫中，既没有观察到向内的力，也没有观察到寄生虫膜的收缩。 TgMIC2 缺陷型寄生虫的运动轨迹不如野生型寄生虫的直线，这表明 TgMIC2 介导的细胞外基质附着的环形区域通常限制了寄生虫在其周围环境中迁移时可用的方向选择。
Toxoplasma gondii is a protozoan parasite that infects 30–40% of the world’s population. Infections are typically subclinical but can be severe and, in some cases, life threatening. Central to the virulence of T. gondii is an unusual form of substrate-dependent motility that enables the parasite to invade cells of its host and to disseminate throughout the body. A hetero-oligomeric complex of proteins that functions in motility has been characterized, but how these proteins work together to drive forward motion of the parasite remains controversial. A key piece of information needed to understand the underlying mechanism(s) is the directionality of the forces that a moving parasite exerts on the external environment. The linear motor model of motility, which has dominated the field for the past two decades, predicts continuous anterior-to-posterior force generation along the length of the parasite. We show here using three-dimensional traction force mapping that the predominant forces exerted by a moving parasite are instead periodic and directed in toward the parasite at a fixed circular location within the extracellular matrix. These highly localized forces, which are generated by the parasite pulling on the matrix, create a visible constriction in the parasite’s plasma membrane. We propose that the ring of inward-directed force corresponds to a circumferential attachment zone between the parasite and the matrix, through which the parasite propels itself to move forward. The combined data suggest a closer connection between the mechanisms underlying parasite motility and host cell invasion than previously recognized. In parasites lacking the major surface adhesin, TgMIC2, neither the inward-directed forces nor the constriction of the parasite membrane are observed. The trajectories of the TgMIC2-deficient parasites are less straight than those of wild-type parasites, suggesting that the annular zone of TgMIC2-mediated attachment to the extracellular matrix normally constrains the directional options available to the parasite as it migrates through its surrounding environment.