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着丝粒的组成和结构在顶复体染色体分离中表现出可塑性。

Composition and organization of kinetochores show plasticity in apicomplexan chromosome segregation.

机构信息

Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Cell Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, Faculty of Science and Engineering, University of Groningen, Groningen, Netherlands.

出版信息

J Cell Biol. 2022 Sep 5;221(9). doi: 10.1083/jcb.202111084. Epub 2022 Aug 25.

DOI:10.1083/jcb.202111084
PMID:36006241
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9418836/
Abstract

Kinetochores are multiprotein assemblies directing mitotic spindle attachment and chromosome segregation. In apicomplexan parasites, most known kinetochore components and associated regulators are apparently missing, suggesting a minimal structure with limited control over chromosome segregation. In this study, we use interactomics combined with deep homology searches to identify 13 previously unknown components of kinetochores in Apicomplexa. Apicomplexan kinetochores are highly divergent in sequence and composition from animal and fungal models. The nanoscale organization includes at least four discrete compartments, each displaying different biochemical interactions, subkinetochore localizations and evolutionary rates across the phylum. We reveal alignment of kinetochores at the metaphase plate in both Plasmodium berghei and Toxoplasma gondii, suggestive of a conserved "hold signal" that prevents precocious entry into anaphase. Finally, we show unexpected plasticity in kinetochore composition and segregation between apicomplexan lifecycle stages, suggestive of diverse requirements to maintain fidelity of chromosome segregation across parasite modes of division.

摘要

着丝粒是指导有丝分裂纺锤体附着和染色体分离的多蛋白复合物。在顶复门寄生虫中，大多数已知的着丝粒成分和相关调节因子显然缺失，这表明存在一个结构简单、对染色体分离的控制有限的着丝粒。在这项研究中，我们使用互作组学结合深度同源搜索，鉴定出了顶复门寄生虫中 13 种以前未知的着丝粒成分。与动物和真菌模型相比，顶复门寄生虫的着丝粒在序列和组成上高度多样化。纳米级组织包括至少四个不同的隔室，每个隔室显示不同的生化相互作用、亚着丝粒定位和整个门的进化速率。我们在疟原虫和刚地弓形虫中都观察到了中期板上的着丝粒对齐，提示存在一个保守的“保持信号”，防止过早进入后期。最后，我们发现顶复门寄生虫生命周期不同阶段的着丝粒组成和分离存在意想不到的可塑性，提示在寄生虫分裂方式中维持染色体分离保真度需要多样化的要求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a15/9418836/923eecc3965c/JCB_202111084_Fig10.jpg
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