结核素定化形成了Leishmania细胞骨架构和毒性
Rosa Milagros Corrales1, Jeremy Vincent1, Lucien Crobu1
1Maladies infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle, University of Montpellier, CNRS, Institut de Recherche pour le Développement, Montpellier 34095, France.
概括
在Leishmania中,由LmVASH调解的tubulin detyrosination对于寄生虫的毒性至关重要. 缺少异化损害了微管的动态,降低了病原性,这表明它是莱什曼病的治疗点.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 寄生虫学的寄生虫学
背景情况:
- 结核素异化调节微管体动力学,并与人类疾病有关.
- 与大多数有机体不同,试素体修改了alpha-和beta-tubulin.
研究的目的:
- 为了研究氨酸强化在莱什曼尼亚病毒性中所起的作用.
- 为了确定负责莱什马尼亚的差异性管氨酸抗化动态的酶.
主要方法:
- 一代LmVASH淘汰Leishmania寄生虫的一代.
- 在淘汰寄生虫中分析蛋白修饰 (脱氧化,谷氨基化).
- 在体内和体外对寄生虫病原性,增殖和形态发生的评估.
- 研究了鞭毛体动力学和相关的运动蛋白.
主要成果:
- 一个单一的酶,lmVASH,控制了莱什马尼亚的α-和β-tubulin的差异性抗氧化.
- 在小鼠中,LMVASH淘汰寄生虫缺乏抗氧化,呈现低谷氨基化,并表现出明显降低的病原性.
- 脱铁素化缺陷导致虫形态变化和鞭缩短,这是由于素-13过活性的原因.
- 减少巨细胞中的寄生虫增殖与病毒毒性降低相关.
结论:
- 结核素bindosination对于莱什马尼亚在哺乳动物宿主中的扩散和毒性至关重要.
- 这项研究确定LmVASH是Leishmania中氨酸异化关键酶.
- 变化的微管动力学,特别是鞭子重塑,对于寄生虫的生存和致病性至关重要.
- 图布林异位化代表了莱什曼病的有前途的治疗标.
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