Wheeler Richard J, Sunter Jack D, Gull Keith
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, Dresden 01307, Germany Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK
Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK
J Cell Sci. 2016 Feb 15;129(4):854-67. doi: 10.1242/jcs.183152. Epub 2016 Jan 8.
Leishmania promastigote parasites have a flagellum, which protrudes from the flagellar pocket at the cell anterior, yet, surprisingly, have homologs of many flagellum attachment zone (FAZ) proteins--proteins used in the related Trypanosoma species to laterally attach the flagellum to the cell body from the flagellar pocket to the cell posterior. Here, we use seven Leishmania mexicana cell lines that expressed eYFP fusions of FAZ protein homologs to show that the Leishmania flagellar pocket includes a FAZ structure. Electron tomography revealed a precisely defined 3D organisation for both the flagellar pocket and FAZ, with striking similarities to those of Trypanosoma brucei. Expression of two T. brucei FAZ proteins in L. mexicana showed that T. brucei FAZ proteins can assemble into the Leishmania FAZ structure. Leishmania therefore have a previously unrecognised FAZ structure, which we show undergoes major structural reorganisation in the transition from the promastigote (sandfly vector) to amastigote (in mammalian macrophages). Morphogenesis of the Leishmania flagellar pocket, a structure important for pathogenicity, is therefore intimately associated with a FAZ; a finding with implications for understanding shape changes involving component modules during evolution.
利什曼原虫前鞭毛体寄生虫有一根鞭毛，从细胞前端的鞭毛袋伸出，然而，令人惊讶的是，它们有许多鞭毛附着区（FAZ）蛋白的同源物——在相关的锥虫物种中用于将鞭毛从鞭毛袋横向附着到细胞体后部的蛋白。在这里，我们使用了七个表达FAZ蛋白同源物的eYFP融合体的墨西哥利什曼原虫细胞系，以表明利什曼原虫的鞭毛袋包含一个FAZ结构。电子断层扫描揭示了鞭毛袋和FAZ精确界定的三维组织，与布氏锥虫的三维组织有惊人的相似之处。在墨西哥利什曼原虫中表达两种布氏锥虫FAZ蛋白表明，布氏锥虫FAZ蛋白可以组装到利什曼原虫的FAZ结构中。因此，利什曼原虫有一个以前未被认识的FAZ结构，我们发现它在从前鞭毛体（沙蝇载体）转变为无鞭毛体（在哺乳动物巨噬细胞中）的过程中经历了重大的结构重组。因此，对致病性很重要的利什曼原虫鞭毛袋的形态发生与一个FAZ密切相关；这一发现对于理解进化过程中涉及组件模块的形状变化具有重要意义。
