Michelle M Shimogawa, Keya Jonnalagadda, Kent L Hill
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引用次数: 0
摘要
布氏锥虫是一种人类和动物病原体,依靠鞭毛运动进行传播和感染。锥虫的鞭毛围绕着一个典型的 "9+2 "轴丝,包含九个双微管(DMT),围绕着两个单微管。每个 DMT 都包含一个 13 根原纤维的 A 管和一个 10 根原纤维的 B 管,并通过一个由 PACRG 和 FAP20 亚基交替组成的保守的非管蛋白内连接(IJ)丝与 A 管连接。在这里,我们研究了原环状布鲁氏菌中的 FAP20。FAP20-NeonGreen融合蛋白如预期一样定位于轴丝。令人惊讶的是,敲除 FAP20 会导致鞭毛组装的灾难性失败,同时导致死亡。这与其他生物不同,在其他生物中,FAP20是鞭毛正常运动所必需的,但对于鞭毛的组装和存活率来说通常是可有可无的。透射电子显微镜显示,FAP20突变体的鞭毛组装失败与一系列DMT缺陷和副鞭毛杆组装缺陷有关,副鞭毛杆是一个品系特异的鞭毛丝,在锥虫中附着在DMT 4-7上。我们的研究揭示了锥虫中对 FAP20 的品系特异性要求,有助于深入了解这些寄生虫对鞭毛稳定性和运动性的适应性,并突出了病原体与宿主的差异,这些差异可用于锥虫疾病的治疗干预。[媒体:见正文] [媒体:见正文]。
FAP20 is required for flagellum assembly in Trypanosoma brucei.
Trypanosoma brucei is a human and animal pathogen that depends on flagellar motility for transmission and infection. The trypanosome flagellum is built around a canonical "9+2" axoneme, containing nine doublet microtubules (DMTs) surrounding two singlet microtubules. Each DMT contains a 13-protofilament A-tubule and a 10-protofilament B-tubule, connected to the A-tubule by a conserved, non-tubulin inner junction (IJ) filament made up of alternating PACRG and FAP20 subunits. Here we investigate FAP20 in procyclic form T. brucei. A FAP20-NeonGreen fusion protein localized to the axoneme as expected. Surprisingly, FAP20 knockdown led to a catastrophic failure in flagellum assembly and concomitant lethality. This differs from other organisms, where FAP20 is required for normal flagellum motility, but generally dispensable for flagellum assembly and viability. Transmission electron microscopy demonstrates failed flagellum assembly in FAP20 mutants is associated with a range of DMT defects and defective assembly of the paraflagellar rod, a lineage-specific flagellum filament that attaches to DMT 4-7 in trypanosomes. Our studies reveal a lineage-specific requirement for FAP20 in trypanosomes, offering insight into adaptations for flagellum stability and motility in these parasites and highlighting pathogen versus host differences that might be considered for therapeutic intervention in trypanosome diseases.
期刊介绍:
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