A cathepsin L protease essential for Caenorhabditis elegans embryogenesis is functionally conserved in parasitic nematodes

A cathepsin L protease essential for Caenorhabditis elegans embryogenesis is functionally conserved in parasitic nematodes
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DOI:
10.1016/s0166-6851(02)00066-x
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发表时间:
2002-06-01
影响因子:
1.5
通讯作者:
Murray, L
Murray, L
中科院分区:
医学4区
文献类型:
--
作者:
Britton, C;Murray, L

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蛋白水解酶参与许多生物体发育和生存的重要过程。寄生虫蛋白酶被认为是寄生虫控制的潜在目标。其精确的生理功能是未知的。潜在目标的确认需要功能分析。我们最近鉴定了一种组织蛋白酶L(CPL)半胱氨酸蛋白酶,Ce-CPL-1。其对于自由生活的线虫秀丽隐杆线虫的胚胎发育是必需的。我们现在表明,CPL基因密切相关的Ce-cpl-1的表达在动物寄生线虫捻转血矛线虫,Dictyocaulus viviparus,Teladorsagia circumcincta,钩虫犬和猪蛔虫,以及在植物寄生线虫。基因结构和编码氨基酸序列的相似性表明,寄生虫和线虫的CPL是同源酶。我们证明了C的损失的功能补偿。通过转基因表达旋毛虫epl-1基因,拯救了线虫cpl-1的胚胎致死性。因此,这些基因可能是直向同源物,在两个物种中具有相同的功能。因此,研究CPL在线虫发育过程中的作用具有重要意义。(C)2002 Elsevier Science B.V,保留所有权利。
Proteolytic enzymes are involved in processes important to development and survival of many organisms. Parasite proteases are considered potential targets of parasite control yet, for most. their precise physiological functions are unknown. Validation of potential targets requires analysis of function. We have recently identified a cathepsin L (CPL) cysteine protease, Ce-CPL-1. which is essential for embryonic development of the free-living nematode Caenorhabditis elegans. We now show that CPL genes closely related to Ce-cpl-1 are expressed in the animal parasitic nematodes Haemonchus contortus, Dictyocaulus viviparus, Teladorsagia circumcincta, Ancylostoma caninum and Ascaris suum, as well as in plant parasitic nematodes. The similarities in gene structure and encoded amino acid sequence indicate that the parasite and C elegans CPLs are homologous enzymes. We demonstrate functional compensation of the loss of C. elegans cpl-1 by transgenic expression of the H, contortus epl-1 gene, rescuing the embryonic lethality. These genes may therefore be orthologues, sharing the same function in both species. Targeting of this enzyme has potential in inhibiting development and transmission of parasitic nematodes, In addition, the role of CPL is important to our understanding of nematode development. (C) 2002 Elsevier Science B.V, All rights reserved.