一种质体锥虫肌动蛋白结合蛋白作为连接蛋白和脂质传感器，协调运动和入侵。

An Apicomplexan Actin-Binding Protein Serves as a Connector and Lipid Sensor to Coordinate Motility and Invasion.

机构信息

Department of Microbiology & Molecular Medicine, University of Geneva, 1 Rue Michel-Servet, 1211 Geneva, Switzerland.

Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7, 90220 Oulu, Finland.

出版信息

Cell Host Microbe. 2016 Dec 14;20(6):731-743. doi: 10.1016/j.chom.2016.10.020.

DOI:10.1016/j.chom.2016.10.020

PMID:27978434

Abstract

Apicomplexa exhibit a unique form of substrate-dependent gliding motility central for host cell invasion and parasite dissemination. Gliding is powered by rearward translocation of apically secreted transmembrane adhesins via their interaction with the parasite actomyosin system. We report a conserved armadillo and pleckstrin homology (PH) domain-containing protein, termed glideosome-associated connector (GAC), that mediates apicomplexan gliding motility, invasion, and egress by connecting the micronemal adhesins with the actomyosin system. TgGAC binds to and stabilizes filamentous actin and specifically associates with the transmembrane adhesin TgMIC2. GAC localizes to the apical pole in invasive stages of Toxoplasma gondii and Plasmodium berghei, and apical positioning of TgGAC depends on an apical lysine methyltransferase, TgAKMT. GAC PH domain also binds to phosphatidic acid, a lipid mediator associated with microneme exocytosis. Collectively, these findings indicate a central role for GAC in spatially and temporally coordinating gliding motility and invasion.

摘要

Apicomplexa 表现出一种独特的基质依赖的滑行运动形式，这对于宿主细胞入侵和寄生虫传播至关重要。滑行运动是由顶端分泌的跨膜黏附蛋白通过与寄生虫肌动球蛋白系统相互作用，向后移位来驱动的。我们报道了一个保守的角蛋白和pleckstrin 同源（PH）结构域蛋白，称为 glideosome-associated connector（GAC），它通过连接微线黏附蛋白与肌动球蛋白系统来介导顶复门生物的滑行运动、入侵和逸出。TgGAC 与丝状肌动蛋白结合并稳定它，并且与跨膜黏附蛋白 TgMIC2 特异性结合。GAC 在刚入侵的 Toxoplasma gondii 和 Plasmodium berghei 中定位于顶端极，并且 TgGAC 的顶端定位依赖于一个顶端赖氨酸甲基转移酶，TgAKMT。GAC PH 结构域也与磷酯酸结合，磷酯酸是一种与微线胞吐作用相关的脂质介质。总的来说，这些发现表明 GAC 在时空上协调滑行运动和入侵中起着核心作用。