Center for Infection and Immunity of Lille, Université Lille Nord de France, Lille, France.
Cell Host Microbe. 2012 May 17;11(5):515-27. doi: 10.1016/j.chom.2012.03.006.
Apicomplexan parasites have an assortment of unique apical secretory organelles (rhoptries and micronemes), which have crucial functions in host infection. Here, we show that a Toxoplasma gondii sortilin-like receptor (TgSORTLR) is required for the subcellular localization and formation of apical secretory organelles. TgSORTLR is a transmembrane protein that resides within Golgi-endosomal related compartments. The lumenal domain specifically interacts with rhoptry and microneme proteins, while the cytoplasmic tail of TgSORTLR recruits cytosolic sorting machinery involved in anterograde and retrograde protein transport. Ectopic expression of the N-terminal TgSORTLR lumenal domain results in dominant negative effects with the mislocalization of both endogenous TgSORTLR as well as rhoptry and microneme proteins. Conditional ablation of TgSORTLR disrupts rhoptry and microneme biogenesis, inhibits parasite motility, and blocks both invasion into and egress from host cells. Thus, the sortilin-like receptor is essential for protein trafficking and the biogenesis of key secretory organelles in Toxoplasma.
顶复门寄生虫具有多种独特的顶端分泌细胞器（棒状体和微线体），这些细胞器在宿主感染中具有重要功能。在这里，我们表明，刚地弓形虫分选连接蛋白样受体（TgSORTLR）是顶端分泌细胞器的亚细胞定位和形成所必需的。TgSORTLR 是一种跨膜蛋白，位于高尔基内体相关隔室中。腔结构域特异性地与棒状体和微线体蛋白相互作用，而 TgSORTLR 的细胞质尾巴招募参与正向和逆向蛋白运输的胞质分选机制。N 端 TgSORTLR 腔结构域的异位表达导致内源性 TgSORTLR 以及棒状体和微线体蛋白的定位错误，表现出显性负效应。TgSORTLR 的条件缺失破坏了棒状体和微线体的生物发生，抑制了寄生虫的运动，并阻止了寄生虫入侵和离开宿主细胞。因此，分选连接蛋白样受体对于刚地弓形虫中蛋白运输和关键分泌细胞器的生物发生是必不可少的。
