Extra-glycosomal localisation of Trypanosoma brucei hexokinase 2.

Extra-glycosomal localisation of Trypanosoma brucei hexokinase 2.
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DOI:
10.1016/j.ijpara.2012.02.008
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发表时间:
2012-04
影响因子:
4
通讯作者:
Morris JC
Morris JC
中科院分区:
医学2区
文献类型:
--
作者:
Joice AC;Lyda TL;Sayce AC;Verplaetse E;Morris MT;Michels PA;Robinson DR;Morris JC

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非洲锥虫中的大多数糖酵解酶都被分隔在类似过氧化物酶体的细胞器——糖质体中。含有过氧化物酶体靶向序列(PTS 1型或2型)的多肽会被靶向这些细胞器。这种靶向作用对寄生虫的生存能力至关重要,因为糖酵解酶的分隔可防止中间代谢物不受调控的依赖ATP的磷酸化。在此,我们报道了一种携带PTS - 2的锥虫己糖激酶TbHK2令人惊讶的糖质体外定位情况。在血流形式的寄生虫中,该蛋白质既定位在糖质体中,也定位在鞭毛上。相关证据包括使用针对天然蛋白质产生的抗血清进行的分级分离和免疫荧光研究,以及对该蛋白质带有表位标签的重组形式的检测。在昆虫阶段的寄生虫中,分布情况不同,该多肽定位在糖质体中且靠近基体。糖质体外蛋白质的功能仍不清楚。虽然它与基体的关联表明它可能在昆虫阶段寄生虫的运动中起作用,但在TbHK2缺失的细胞中未观察到细胞运动方向或速度有可检测到的缺陷,这表明该蛋白质在细胞中可能具有不同的功能。
The majority of the glycolytic enzymes in the African trypanosome are compartmentalized within peroxisome-like organelles, the glycosomes. Polypeptides harboring peroxisomal targeting sequences (PTS type 1 or 2) are targeted to these organelles. This targeting is essential to parasite viability, as compartmentalization of glycolytic enzymes prevents unregulated ATP-dependent phosphorylation of intermediatemetabolites. Here, we report the surprising extra-glycosomal localization of aPTS-2 bearing trypanosomal hexokinase, TbHK2. In bloodstream form parasites, the protein localizes to both glycosomes and to the flagellum. Evidence for this includes fractionation and immunofluorescence studies using antisera generated against the authentic protein as well as detection of epitope-tagged recombinant versions of the protein. In the insect stage parasite, distribution is different, with the polypeptide localized to glycosomes and proximal to the basal bodies. The function of the extra-glycosomal protein remains unclear. While its association with the basal body suggests that it may have a role in locomotion in the insect stage parasite, no detectable defect indirectional motility or velocity of cell movement were observed for TbHK2-deficient cells, suggesting that protein may have a different function in the cell.
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