The apical complex provides a regulated gateway for secretion of invasion factors in Toxoplasma.
The apical complex provides a regulated gateway for secretion of invasion factors in Toxoplasma.
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DOI：
10.1371/journal.ppat.1004074
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发表时间：
2014-04
期刊：
影响因子：
6.7
通讯作者：
Waller RF
中科院分区：
文献类型：
--
作者：
Katris NJ;van Dooren GG;McMillan PJ;Hanssen E;Tilley L;Waller RF
顶复合体是顶复合体门的决定性细胞结构，是寄主细胞渗透和建立细胞内寄生的焦点。尽管这种结构很重要，但人们对其分子组成知之甚少，很少有研究通过实验测试其功能。我们已经鉴定了一种新的刚地弓形虫蛋白RNG2，它位于根尖极性环——根尖复合物的常见结构元素。在细胞分裂过程中，RNG2在中心体复制后立即被招募到中心体中，这证实了新的顶复合体的组装是细胞复制最早的事件之一。RNG2随后形成一个环，羧基端和氨基端分别固定在顶端极环和可移动的圆锥体上，连接这两个结构。超分辨率显微镜分析了这两个末端，发现当锥体被挤压时，RNG2取向在侵入过程中发生翻转。诱导下调RNG2可强烈抑制宿主细胞的侵袭。与此一致的是，在缺乏RNG2的情况下，微素的分泌被阻止。然而，这种阻滞可以通过外源刺激钙或cGMP信号通路来完全或部分克服，这表明顶复合体直接参与了这些信号通路。RNG2首次在这一重要寄生虫群中证实了顶复合体在控制入侵因子分泌中的作用。顶复合体寄生虫包括主要的人类病原体，包括引起疟疾的寄生虫疟原虫和导致出生缺陷和神经系统疾病的刚地弓形虫。这个群体成功的关键是顶端复合体的进化，这是宿主细胞入侵事件的焦点结构。这种结构最近被证明是由鞭毛器官的元素衍生而来的，在相关的原生生物中，一个根尖复合体的雏形用于取食。顶复合体寄主细胞入侵的进化需要从细胞顶端协调分泌入侵因子。然而，在入侵过程中，对顶端复合体成分的行为或功能知之甚少。我们已经鉴定了一种新的蛋白质RNG2，它在弓形虫的根尖复合体的中心形成一个环。这是一个连接可移动的圆锥体和顶极环的动态环，是复制寄生虫的第一个结构之一。当RNG2被人为地耗尽时，细胞对分泌的分子信号变得不敏感，并且入侵宿主细胞被阻止。这表明，顶复合体直接参与调节分泌，控制入侵事件。
The apical complex is the definitive cell structure of phylum Apicomplexa, and is the focus of the events of host cell penetration and the establishment of intracellular parasitism. Despite the importance of this structure, its molecular composition is relatively poorly known and few studies have experimentally tested its functions. We have characterized a novel Toxoplasma gondii protein, RNG2, that is located at the apical polar ring—the common structural element of apical complexes. During cell division, RNG2 is first recruited to centrosomes immediately after their duplication, confirming that assembly of the new apical complex commences as one of the earliest events of cell replication. RNG2 subsequently forms a ring, with the carboxy- and amino-termini anchored to the apical polar ring and mobile conoid, respectively, linking these two structures. Super-resolution microscopy resolves these two termini, and reveals that RNG2 orientation flips during invasion when the conoid is extruded. Inducible knockdown of RNG2 strongly inhibits host cell invasion. Consistent with this, secretion of micronemes is prevented in the absence of RNG2. This block, however, can be fully or partially overcome by exogenous stimulation of calcium or cGMP signaling pathways, respectively, implicating the apical complex directly in these signaling events. RNG2 demonstrates for the first time a role for the apical complex in controlling secretion of invasion factors in this important group of parasites. Apicomplexan parasites comprise major human pathogens, including the malaria-causing parasites Plasmodium spp., and Toxoplasma gondii that causes birth defects and neurological disorders. Key to the success of this group was the evolution of the apical complex, a structure at the focus of the events of host cell invasion. This structure was recently shown to derive from elements of the flagellar apparatus, and rudiments of an apical complex are used for feeding in related protists. Evolution of host cell invasion in Apicomplexa has entailed development of a coordinated secretion of invasion factors from the cell apex. Little is known, however, of the behaviour or function of the components of the apical complex during invasion. We have characterized a new protein, RNG2, that forms a ring at the heart of the apical complex in T. gondii. This is a dynamic ring that links the mobile conoid with the apical polar ring, and is assembled as one of the first structures in replicating parasites. When RNG2 is artificially depleted, cells become insensitive to the molecular cues for secretion, and invasion of host cells is blocked. This reveals that the apical complex participates directly in regulating secretion, and controlling the events of invasion.
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影响因子：
3.7
作者：
Behnke MS;Wootton JC;Lehmann MM;Radke JB;Lucas O;Nawas J;Sibley LD;White MW
通讯作者：
White MW
弓形虫 IMC 蛋白的一个新家族在协调寄生虫分裂中表现出层次结构和功能。
影响因子：
6.7
作者：
Beck, Josh R.;Rodriguez-Fernandez, Imilce A.;de Leon, Jessica Cruz;Huynh, My-Hang;Carruthers, Vern B.;Morrissette, Naomi S.;Bradley, Peter J.
通讯作者：
Bradley, Peter J.
影响因子：
48
作者：
Andenmatten, Nicole;Egarter, Saskia;Jackson, Allison J;Jullien, Nicolas;Herman, Jean-Paul;Meissner, Markus
通讯作者：
Meissner, Markus
影响因子：
4
作者：
Gubbels MJ;Duraisingh MT
通讯作者：
Duraisingh MT
影响因子：
30.3
作者：
Billker O;Lourido S;Sibley LD
通讯作者：
Sibley LD