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血流形式上调蛋白的亚细胞蛋白质定位描绘了阶段特异性适应。

Subcellular protein localisation of bloodstream form-upregulated proteins maps stage-specific adaptations.

作者信息

Halliday Clare, Dean Samuel, Sunter Jack Daniel, Wheeler Richard J

机构信息

Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK.

出版信息

Wellcome Open Res. 2023 May 23;8:46. doi: 10.12688/wellcomeopenres.18586.2. eCollection 2023.

Abstract

Genome-wide subcellular protein localisation in through our TrypTag project, has comprehensively dissected the molecular organisation of this important pathogen. Powerful as this resource is has multiple developmental forms and we previously only analysed the procyclic form. This is an insect life cycle stage, leaving the mammalian bloodstream form unanalysed. The expectation is that between life stages protein localisation would not change dramatically (completely unchanged or shifting to analogous stage-specific structures). However, this has not been specifically tested. Similarly, which organelles tend to contain proteins with stage-specific expression can be predicted from known stage specific adaptations but has not been comprehensively tested. We used endogenous tagging with mNG to determine the sub-cellular localisation of the majority of proteins encoded by transcripts significantly upregulated in the bloodstream form, and performed comparison to the existing localisation data in procyclic forms. We have confirmed the localisation of known stage-specific proteins and identified the localisation of novel stage-specific proteins. This gave a map of which organelles tend to contain stage specific proteins: the mitochondrion for the procyclic form, and the endoplasmic reticulum, endocytic system and cell surface in the bloodstream form. This represents the first genome-wide map of life cycle stage-specific adaptation of organelle molecular machinery in .

摘要

通过我们的TrypTag项目对全基因组亚细胞蛋白质定位进行研究,已经全面剖析了这种重要病原体的分子组织。尽管这个资源很强大,但该病原体有多种发育形式,而我们之前只分析了前循环形式。这是昆虫生命周期的一个阶段,未对哺乳动物血液阶段形式进行分析。预期是在不同生命阶段之间蛋白质定位不会发生显著变化(完全不变或转移到类似的阶段特异性结构)。然而,这一点尚未经过专门测试。同样,可以根据已知的阶段特异性适应性预测哪些细胞器倾向于包含具有阶段特异性表达的蛋白质,但尚未进行全面测试。我们使用mNG进行内源性标记,以确定在血液阶段形式中显著上调的转录本所编码的大多数蛋白质的亚细胞定位,并与前循环形式中现有的定位数据进行比较。我们已经证实了已知阶段特异性蛋白质的定位,并确定了新的阶段特异性蛋白质的定位。这给出了一张哪些细胞器倾向于包含阶段特异性蛋白质的图谱:前循环形式是线粒体,血液阶段形式是内质网、内吞系统和细胞表面。这代表了在该病原体中细胞器分子机制生命周期阶段特异性适应性的首张全基因组图谱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273d/10209627/25ead204905f/wellcomeopenres-8-21501-g0000.jpg

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