Proteasome activity is required for the stage-specific transformation of a protozoan parasite.
Proteasome activity is required for the stage-specific transformation of a protozoan parasite.
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DOI：
10.1084/jem.184.5.1909
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发表时间：
1996-11-01
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细胞内寄生虫的生命周期的一个突出特征是它们在脊椎动物和无脊椎动物宿主中发育期间经历的深刻的形态变化。在真核细胞中，大多数细胞质蛋白在蛋白酶体中降解。在这里，我们表明，在无菌介质中的克氏锥虫锥鞭毛体转化为无鞭毛体样生物，和寄生虫的细胞内发育从无鞭毛体到锥鞭毛体，被阻止lactacystin，或肽醛，抑制蛋白酶体功能。一种无活性的lactacystin类似物Clasto-lactacystin和T. Cruzi半胱氨酸蛋白酶没有作用。我们还鉴定了T. cruzi作为lactacystin的体内靶点。我们的研究结果文件中的原生动物的阶段特异性转化的蛋白酶体的重要作用。
A prominent feature of the life cycle of intracellular parasites is the profound morphological changes they undergo during development in the vertebrate and invertebrate hosts. In eukaryotic cells, most cytoplasmic proteins are degraded in proteasomes. Here, we show that the transformation in axenic medium of trypomastigotes of Trypanosoma cruzi into amastigote-like organisms, and the intracellular development of the parasite from amastigotes into trypomastigotes, are prevented by lactacystin, or by a peptide aldehyde that inhibits proteasome function. Clasto-lactacystin, an inactive analogue of lactacystin, and cell-permeant peptide aldehyde inhibitors of T. cruzi cysteine proteinases have no effect. We have also identified the 20S proteasomes from T. cruzi as a target of lactacystin in vivo. Our results document the essential role of proteasomes in the stage-specific transformation of a protozoan.