A retromerlike complex is a novel Rab7 effector that is involved in the transport of the virulence factor cysteine protease in the enteric protozoan parasite Entamoeba histolytica
A retromerlike complex is a novel Rab7 effector that is involved in the transport of the virulence factor cysteine protease in the enteric protozoan parasite Entamoeba histolytica
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DOI：
10.1091/mbc.e05-04-0283
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发表时间：
2005-11-01
影响因子：
3.3
通讯作者：
Nozaki, T
中科院分区：
文献类型：
--
作者：
Nakada-Tsukui, K;Saito-Nakano, Y;Nozaki, T
囊泡运输在肠道原生动物寄生虫溶组织内阿米巴的毒力机制中发挥着重要作用，因为分泌的溶酶体半胱氨酸蛋白酶（CP）有助于组织的细胞溶解和内化宿主细胞的降解。尽管细胞内分选在发病机制中具有首要重要性，但 CP 运输的分子机制仍然很大程度上未知。在本报告中，我们证明 CP 的转运是通过 Rab7A 小 GTP 酶 (EhRab7A) 与逆转录酶样复合物的特异性相互作用来调节的。由 Vps26、Vps29 和 Vps35 组成的阿米巴逆转录酶样复合物被鉴定为 EhRab7A 结合蛋白。阿米巴逆转录酶样复合物通过 EhVps26 的羧基末端直接结合，特异性结合 GTP-EhRab7A，但不结合 GDP-EhRab7A。在红细胞吞噬作用中，逆转录酶样复合物被募集到吞噬体前液泡（消化酶的独特预备液泡），然后被募集到吞噬体。这种活力与 EhRab7A 的活力没有区别，并且与逆转录酶样复合物参与假定的水解酶受体从预备液泡和吞噬体到高尔基体的逆行转运的前提一致。 EhRab7A 过度表达导致溶酶体增大和细胞 CP 活性降低。降低的 CP 活性通过 EhVps26 的共表达得以恢复，这意味着 EhRab7A 介导的 CP 向吞噬体的转运受到类逆转录酶复合物的调节。
Vesicular trafficking plays an important role in a virulence mechanism of the enteric protozoan parasite Entamoeba histolytica as secreted and lysosomal cysteine protease (CP) contributes to both cytolysis of tissues and degradation of internalized host cells. Despite the primary importance of intracellular sorting in pathogenesis, the molecular mechanism of CP trafficking remains largely unknown. In this report we demonstrate that transport of CP is regulated through a specific interaction of Rab7A small GTPase (EhRab7A) with the retromerlike complex. The amoebic retromerlike complex composed of Vps26, Vps29, and Vps35 was identified as EhRab7A-binding proteins. The amoebic retromerlike complex specifically bound to GTP-EhRab7A, but not GDP-EhRab7A through the direct binding via the carboxy terminus of EhVps26. In erythrophagocytosis the retromerlike complex was recruited to prephagosomal vacuoles, the unique preparatory vacuole of digestive enzymes, and later to phagosomes. This dynamism was indistinguishable from that of EhRab7A, and consistent with the premise that the retromerlike complex is involved in the retrograde transport of putative hydrolase receptor(s) from preparatory vacuoles and phagosomes to the Golgi apparatus. EhRab7A overexpression caused enlargement of lysosomes and decrease of the cellular CP activity. The reduced CP activity was restored by the coexpression of EhVps26, implying that the EhRab7A-mediated transport of CP to phagosomes is regulated by the retromerlike complex.