Identification and characterization of an escorter for two secretory adhesins in Toxoplasma gondii.

Identification and characterization of an escorter for two secretory adhesins in Toxoplasma gondii.
复制标题

在弓形虫弓形虫中的两个分泌粘合剂的培训者的鉴定和表征。

DOI:
10.1083/jcb.152.3.563
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发表时间:
2001-02-05
影响因子:
7.8
通讯作者:
Soldati, D
Soldati, D
中科院分区:
生物学1区
文献类型:
--
作者:
Reiss, M;Viebig, N;Brecht, S;Fourmaux, M N;Soete, M;Di Cristina , M;Dubremetz, J F;Soldati, D

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细胞内原生动物寄生虫弓形虫与顶复门的其他成员共享一组共同的参与宿主细胞侵入的顶端结构。花丝是顶端分泌细胞器,在与宿主细胞接触时释放其内容物。我们已经确定了一个跨膜微线蛋白MIC6,其功能作为一个护送器的两个可溶性蛋白MIC1和MIC4的精确靶向的微线。MIC1、MIC4和MIC6基因的破坏使我们能够精确地剖析它们在分选过程中的贡献。我们已经绘制了这些蛋白质上的结构域,这些结构域决定了复合物的形成和靶向细胞器。MIC6在其胞质尾区携带分选信号,而其与MIC1的结合涉及内腔EGF样结构域。MIC4直接与MIC1结合,并表现为被动货物分子。相比之下,MIC1与质量控制系统相关,并且是复合物离开分泌途径的早期隔室所绝对需要的。MIC1和MIC4与宿主细胞结合,这种复合物的存在提供了解释可溶性粘附素如何起作用的合理机制。我们假设在入侵过程中,MIC6沿着粘附素在宿主细胞和寄生虫之间建立了一座桥梁。
The intracellular protozoan parasite Toxoplasma gondii shares with other members of the Apicomplexa a common set of apical structures involved in host cell invasion. Micronemes are apical secretory organelles releasing their contents upon contact with host cells. We have identified a transmembrane micronemal protein MIC6, which functions as an escorter for the accurate targeting of two soluble proteins MIC1 and MIC4 to the micronemes. Disruption of MIC1, MIC4, and MIC6 genes allowed us to precisely dissect their contribution in sorting processes. We have mapped domains on these proteins that determine complex formation and targeting to the organelle. MIC6 carries a sorting signal(s) in its cytoplasmic tail whereas its association with MIC1 involves a lumenal EGF-like domain. MIC4 binds directly to MIC1 and behaves as a passive cargo molecule. In contrast, MIC1 is linked to a quality control system and is absolutely required for the complex to leave the early compartments of the secretory pathway. MIC1 and MIC4 bind to host cells, and the existence of such a complex provides a plausible mechanism explaining how soluble adhesins act. We hypothesize that during invasion, MIC6 along with adhesins establishes a bridge between the host cell and the parasite.