Toxoplasma Sortilin-like Receptor Regulates Protein Transport and Is Essential for Apical Secretory Organelle Biogenesis and Host Infection
Toxoplasma Sortilin-like Receptor Regulates Protein Transport and Is Essential for Apical Secretory Organelle Biogenesis and Host Infection
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DOI：
10.1016/j.chom.2012.03.006
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发表时间：
2012-05-17
影响因子：
30.3
通讯作者：
Tomavo, Stanislas
中科院分区：
文献类型：
--
作者：
Sloves, Pierre-Julien;Delhaye, Stephane;Tomavo, Stanislas
顶复门寄生虫有一个独特的顶端分泌细胞器（棒状体和微丝）的分类，在宿主感染中具有重要的功能。在这里，我们表明，弓形虫分拣蛋白样受体（TgSORTLR）是必需的亚细胞定位和顶端分泌细胞器的形成。TgSORTLR是一种跨膜蛋白，位于高尔基体-内体相关区室内。内腔结构域特异性地与棒状体和微线体蛋白相互作用，而TgSORTLR的胞质尾区招募参与顺行和逆行蛋白质转运的胞质分选机制。N-末端TgSORTLR内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错误定位的显性负效应。TgSORTLR的条件性消融破坏棒状体和微线体生物发生，抑制寄生虫运动，并阻断侵入宿主细胞和从宿主细胞外出。因此，分拣蛋白样受体是必不可少的蛋白质运输和弓形虫的关键分泌细胞器的生物合成。
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.