Cysteine peptidases CPA and CPB are vital for autophagy and differentiation in Leishmania mexicana
Cysteine peptidases CPA and CPB are vital for autophagy and differentiation in Leishmania mexicana
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DOI：
10.1111/j.1365-2958.2006.05274.x
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发表时间：
2006-08
影响因子：
3.6
通讯作者：
R. A. Williams;L. Tetley;J. Mottram;G. H. Coombs
中科院分区：
文献类型：
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作者：
R. A. Williams;L. Tetley;J. Mottram;G. H. Coombs
在过去，墨西哥利什曼原虫无鞭毛体的超微结构研究揭示了被暂时确定为自噬体的结构。这项研究现在提供了明确的数据，自噬发生在寄生虫在分化为后环前鞭毛体和无鞭毛体，自噬体是特别多的后环无鞭毛体的形式转换期间。此外，结果表明，抑制两种主要的溶酶体半胱氨酸肽酶（CPA和CPB）或去除它们的基因不仅干扰自噬途径，而且还防止元循环和转化为无鞭毛体，从而增加了对自噬是细胞分化所需的假设的支持。研究表明L. mexicana CPA和CPB在酿酒酵母中与天冬氨酸肽酶PEP 4和丝氨酸肽酶PRB 1起类似的作用。这一结果也解释了为什么L. mexicana CPA/CPB缺陷型突变体转化为无鞭毛体的能力非常差，并且在巨噬细胞和小鼠中缺乏毒力。
In the past, ultrastructural investigations of Leishmania mexicana amastigotes revealed structures that were tentatively identified as autophagosomes. This study has now provided definitive data that autophagy occurs in the parasite during differentiation both to metacyclic promastigotes and to amastigotes, autophagosomes being particularly numerous during metacyclic to amastigote form transformation. Moreover, the results demonstrate that inhibiting two major lysosomal cysteine peptidases (CPA and CPB) or removing their genes not only interferes with the autophagy pathway but also prevents metacyclogenesis and transformation to amastigotes, thus adding support to the hypothesis that autophagy is required for cell differentiation. The study suggests that L. mexicana CPA and CPB perform similar roles to the aspartic peptidase PEP4 and the serine peptidase PRB1 in Saccharomyces cerevisiae. The results also provide an explanation for why L. mexicana CPA/CPB‐deficient mutants transform to amastigotes very poorly and lack virulence in macrophages and mice.