Leung Jacqueline M, He Yudou, Zhang Fangliang, Hwang Yu-Chen, Nagayasu Eiji, Liu Jun, Murray John M, Hu Ke
Department of Biology, Indiana University, Bloomington, IN 47405.
Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33136.
Mol Biol Cell. 2017 May 15;28(10):1361-1378. doi: 10.1091/mbc.E17-01-0045. Epub 2017 Mar 22.
The organization of the microtubule cytoskeleton is dictated by microtubule nucleators or organizing centers. , an important human parasite, has an array of 22 regularly spaced cortical microtubules stemming from a hypothesized organizing center, the apical polar ring. Here we examine the functions of the apical polar ring by characterizing two of its components, KinesinA and APR1, and show that its putative role in templating can be separated from its mechanical stability. Parasites that lack both KinesinA and APR1 () are capable of generating 22 cortical microtubules. However, the apical polar ring is fragmented in live parasites and is undetectable by electron microscopy after detergent extraction. Disintegration of the apical polar ring results in the detachment of groups of microtubules from the apical end of the parasite. These structural defects are linked to a diminished ability of the parasite to move and invade host cells, as well as decreased secretion of effectors important for these processes. Together the findings demonstrate the importance of the structural integrity of the apical polar ring and the microtubule array in the lytic cycle, which is responsible for massive tissue destruction in acute toxoplasmosis.
微管细胞骨架的组织由微管成核剂或组织中心决定。弓形虫是一种重要的人体寄生虫，有一系列22根规则间隔的皮质微管，这些微管起源于一个假定的组织中心——顶端极环。在这里，我们通过表征顶端极环的两个组成部分驱动蛋白A和APR1来研究其功能，并表明其在模板形成中的假定作用可以与其机械稳定性分开。同时缺乏驱动蛋白A和APR1的寄生虫（ ）能够产生22根皮质微管。然而，顶端极环在活的 寄生虫中是破碎的，并且在去污剂提取后通过电子显微镜无法检测到。顶端极环的解体导致微管组从寄生虫的顶端脱离。这些结构缺陷与寄生虫移动和侵入宿主细胞的能力减弱有关，也与对这些过程重要的效应物分泌减少有关。这些发现共同证明了顶端极环和微管阵列的结构完整性在弓形虫裂解周期中的重要性，弓形虫裂解周期在急性弓形虫病中导致大量组织破坏。
