Rab11B small GTPase regulates secretion of cysteine proteases in the enteric protozoan parasite Entamoeba histolytica
Rab11B small GTPase regulates secretion of cysteine proteases in the enteric protozoan parasite Entamoeba histolytica
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DOI：
10.1111/j.1462-5822.2007.00941.x
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发表时间：
2007-09-01
影响因子：
3.4
通讯作者：
Nozaki, Tomoyoshi
中科院分区：
文献类型：
--
作者：
Mitra, Biswa Nath;Saito-Nakano, Yumiko;Nozaki, Tomoyoshi
囊泡运输在肠道原生动物寄生虫溶组织内阿米巴的毒力中起着关键作用。在本研究中，我们发现，一个同型的小GTTRab11，EhRab11B，在一个主要的毒力因子，半胱氨酸蛋白酶的分泌起着核心作用。EhRab11B没有与内质网、早期内体和溶酶体的标记物共定位，但与内吞途径中的非酸化囊泡部分相关，可能是再循环内体。EhRab11B的过表达导致细胞内和分泌的半胱氨酸蛋白酶活性显著增加，伴随着细胞溶解活性的增强，如通过增加破坏哺乳动物细胞的能力所证明的。具有EhRab11B过表达的半胱氨酸蛋白酶的过度分泌对布雷菲德菌素A既不敏感，也不特异于某些半胱氨酸蛋白酶种类（例如CP 1、2或5），表明这三种主要的半胱氨酸蛋白酶通过EhRab11B相关的分泌途径被运输，这与经典的布雷菲德菌素敏感途径不同。EhRab11B的过表达也增强了掺入的液相标记物的胞吐作用，支持了它参与回收的观点。这是第一份证明Rab11在致病因子的运输和分泌中发挥核心作用的报告。
Vesicular trafficking plays a pivotal role in the virulence of the enteric protozoan parasite Entamoeba histolytica. In the present study, we showed that one isotype of the small GTPase Rab11, EhRab11B, plays a central role in the secretion of a major virulence factor, cysteine proteases. EhRab11B did not colocalize with markers for the endoplasmic reticulum, early endosomes and lysosomes, but was partially associated with non-acidified vesicles in the endocytic pathway, likely recycling endosomes. Overexpression of EhRab11B resulted in a remarkable increase in both intracellular and secreted cysteine protease activity, concomitant with an augmentation of cytolytic activity as demonstrated by an increased ability to destroy mammalian cells. The oversecretion of cysteine proteases with EhRab11B overexpression was neither sensitive to brefeldin A nor specific to a certain cysteine protease species (e.g. CP1, 2 or 5), suggesting that these three major cysteine proteases are trafficked via an EhRab11B-associated secretory pathway, which is distinct from the classical brefeldin-sensitive pathway. Overexpression of EhRab11B also enhanced exocytosis of the incorporated fluid-phase marker, supporting the notion that it is involved in recycling. This is the first report demonstrating that Rab11 plays a central role in the transport and secretion of pathogenic factors.