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Cell Morphogenesis of Trypanosoma brucei Requires the Paralogous, Differentially Expressed Calpain-related Proteins CAP5.5 and CAP5.5V

机译:布氏锥虫的细胞形态发生需要同源,差异表达的钙蛋白酶相关蛋白CAP5.5和CAP5.5V

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摘要

Proteins from the calpain super-family are involved in developmentally- and environmentally regulated re-modelling of the eukaryotic cytoskeleton and the dynamic organisation of signal transduction cascades. In trypanosomatid parasites, calpain-related gene families are unusually large, but we have little insight in to the functional roles played by these molecules during trypanosomatid lifecycles. Here we report that CAP5.5, a cytoskeletal calpain-related protein subject to strict stage-specific expression in the sleeping sickness parasite Trypanosoma brucei, is essential and required for correct cell morphogenesis of procyclic (tsetse mid-gut stage) T. brucei. Striking consequences of CAP5.5 RNA interference are the loss of protein from the posterior cell-end, organelle mis-positioning giving rise to aberrant cytokinesis, and disorganisation of the sub-pellicular microtubules that define trypanosome cell shape. We further report that the stage-specificity of CAP5.5 expression can be explained by the presence of a paralogue, CAP5.5V, which is required for cell morphogenesis in bloodstream T. brucei; RNAi against this paralogous protein results in a qualitatively similar phenotype to that described for procyclic CAP5.5 RNAi mutants. By comparison to recently described phenotypes for other procyclic trypanosome RNAi mutants, likely functions for CAP5.5 and CAP5.5V are discussed.
机译:钙蛋白酶超家族的蛋白质参与了真核细胞骨架的发育和环境调控的重塑以及信号转导级联的动态组织。在锥虫的寄生虫中,钙蛋白酶相关的基因家族异常大,但是我们对锥虫在生命周期中这些分子发挥的功能性作用知之甚少。在这里我们报道,CAP5.5,一种细胞骨架钙蛋白酶相关蛋白,在昏睡病原虫布氏锥虫中有严格的阶段特异性表达,对于正确的前循环(采采蝇中肠阶段)布氏锥虫细胞形态发生是必不可少的。 CAP5.5 RNA干扰的显着后果是细胞后部蛋白质丢失,细胞器错位导致异常的胞质分裂和定义锥虫体细胞形状的膜下微管的混乱。我们进一步报道,CAP5.5表达的阶段特异性可以通过存在类似物CAP5.5V来解释,这是血液T. brucei中细胞形态发生所必需的。针对这种旁系蛋白的RNAi与定性CAP5.5 RNAi突变体的表型在质上相似。通过与最近描述的其他前环锥虫RNAi突变体的表型进行比较,讨论了CAP5.5和CAP5.5V的可能功能。

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