Sato Dan, Nakada-Tsukui Kumiko, Okada Mami, Nozaki Tomoyoshi
Department of Parasitology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
FEBS Lett. 2006 Oct 2;580(22):5306-12. doi: 10.1016/j.febslet.2006.08.081. Epub 2006 Sep 12.
The enteric protozoan parasite Entamoeba histolytica uniquely possesses two isotypes of ICPs, a novel class of inhibitors for cysteine proteases. These two EhICPs showed a remarkable difference in the ability to inhibit cysteine protease (CP) 5, a well-established virulence determinant, whereas they equally inhibited CP1 and CP2. Immunofluorescence imaging and cellular fractionation showed that EhICP1 and EhICP2 are localized to distinct compartments. While EhICP1 is localized to the soluble cytosolic fraction, EhICP2 is targeted from lysosomes to phagosomes upon erythrocyte engulfment. Overexpression of either EhICP1 or EhICP2 caused reduction of intracellular CP activity, but not the amount of CP, and decrease in the secretion of all major CPs, suggesting that both EhICPs are involved in the trafficking and/or interference with the major CP activity. These data indicate that the two EhICPs, present in distinct subcellular compartments, negatively regulate CP secretion, and, thus, the virulence of this parasite.
肠道原生动物寄生虫溶组织内阿米巴独特地拥有两种类型的肠胱抑素（ICPs），这是一类新型的半胱氨酸蛋白酶抑制剂。这两种溶组织内阿米巴肠胱抑素（EhICPs）在抑制半胱氨酸蛋白酶（CP）5方面表现出显著差异，CP5是一种公认的毒力决定因素，而它们对CP1和CP2的抑制作用相同。免疫荧光成像和细胞分级分离表明，EhICP1和EhICP2定位于不同的区室。虽然EhICP1定位于可溶性胞质部分，但在吞噬红细胞后，EhICP2从溶酶体靶向至吞噬体。过表达EhICP1或EhICP2都会导致细胞内CP活性降低，但不会降低CP的量，并且所有主要CP的分泌都会减少，这表明两种EhICPs都参与了主要CP活性的运输和/或干扰。这些数据表明，存在于不同亚细胞区室中的两种EhICPs对CP分泌起负调节作用，从而对该寄生虫的毒力起负调节作用。
