Conservation and divergence within the clathrin interactome of Trypanosoma cruzi.

Conservation and divergence within the clathrin interactome of Trypanosoma cruzi.
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克氏锥虫凝集素相互作用组的保存和分化。

DOI:
10.1038/srep31212
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发表时间:
2016-08-09
期刊:
影响因子:
4.6
通讯作者:
Field MC
Field MC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kalb LC;Frederico YC;Boehm C;Moreira CM;Soares MJ;Field MC

文献摘要

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锥虫是一种寄生性原虫,严重危害人类健康。非洲和美洲锥虫分别是Nagana病和Chagas病的病原体,大约在3亿年前形成。这些寄生虫具有高度不同的生命周期,病理,传播策略和表面蛋白质组,分别由变体表面糖蛋白(非洲)或粘蛋白(美国)主导。在非洲锥虫网格蛋白介导的贩运是负责内吞作用和后高尔基体运输,有几个方面的机械不同于高等生物。使用网格蛋白轻链(TcCLC)和EpsinR(TcEpsinR)作为亲和手柄,我们确定了克氏锥虫中的候选网格蛋白相关蛋白(CAP);该队列包括已知介导囊泡运输的许多蛋白质的直系同源物,但明显不是AP-2接头复合物。还鉴定了几种与非洲锥虫共同的锥虫特异性蛋白。荧光显微镜显示定位TcEpsinR,TcCLC和TcCHC在锥虫鞭毛体细胞的后部区域,与鞭毛袋和高尔基体相一致。这些数据提供了第一个系统的分析网格蛋白介导的运输T。cruzi,允许蛋白质队列和其他锥虫之间的比较,也表明网格蛋白运输在至少一些生活阶段的锥虫。cruzi可以是AP-2独立的。
Trypanosomatids are parasitic protozoa with a significant burden on human health. African and American trypanosomes are causative agents of Nagana and Chagas disease respectively, and speciated about 300 million years ago. These parasites have highly distinct life cycles, pathologies, transmission strategies and surface proteomes, being dominated by the variant surface glycoprotein (African) or mucins (American) respectively. In African trypanosomes clathrin-mediated trafficking is responsible for endocytosis and post-Golgi transport, with several mechanistic aspects distinct from higher organisms. Using clathrin light chain (TcCLC) and EpsinR (TcEpsinR) as affinity handles, we identified candidate clathrin-associated proteins (CAPs) in Trypanosoma cruzi; the cohort includes orthologs of many proteins known to mediate vesicle trafficking, but significantly not the AP-2 adaptor complex. Several trypanosome-specific proteins common with African trypanosomes, were also identified. Fluorescence microscopy revealed localisations for TcEpsinR, TcCLC and TcCHC at the posterior region of trypomastigote cells, coincident with the flagellar pocket and Golgi apparatus. These data provide the first systematic analysis of clathrin-mediated trafficking in T. cruzi, allowing comparison between protein cohorts and other trypanosomes and also suggest that clathrin trafficking in at least some life stages of T. cruzi may be AP-2-independent.