Williams Roderick A, Tetley Laurence, Mottram Jeremy C, Coombs Graham H
Division of Infection and Immunity, Institute of Biomedical and Life Sciences and Wellcome Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
Mol Microbiol. 2006 Aug;61(3):655-74. doi: 10.1111/j.1365-2958.2006.05274.x. Epub 2006 Jun 27.
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.
过去，对墨西哥利什曼原虫无鞭毛体的超微结构研究揭示了一些结构，这些结构被初步鉴定为自噬体。这项研究现已提供了确凿的数据，表明自噬在寄生虫向循环前鞭毛体和无鞭毛体分化的过程中都会发生，在循环前鞭毛体向无鞭毛体形态转变过程中自噬体尤其众多。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会干扰自噬途径，还会阻止循环前鞭毛体的形成以及向无鞭毛体的转变，从而为自噬是细胞分化所必需的这一假说提供了支持。该研究表明，墨西哥利什曼原虫的CPA和CPB与酿酒酵母中的天冬氨酸肽酶PEP4和丝氨酸肽酶PRB1发挥着相似的作用。这些结果还解释了为什么墨西哥利什曼原虫CPA/CPB缺陷型突变体向无鞭毛体的转变非常差，并且在巨噬细胞和小鼠中缺乏毒力。
