D'Archivio Simon, Wickstead Bill
School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, England, UK.
School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, England, UK
J Cell Biol. 2017 Feb;216(2):379-391. doi: 10.1083/jcb.201608043. Epub 2016 Dec 29.
Kinetochores are multiprotein complexes that couple eukaryotic chromosomes to the mitotic spindle to ensure proper segregation. The model for kinetochore assembly is conserved between humans and yeast, and homologues of several components are widely distributed in eukaryotes, but key components are absent in some lineages. The recent discovery in a lineage of protozoa called kinetoplastids of unconventional kinetochores with no apparent homology to model organisms suggests that more than one system for eukaryotic chromosome segregation may exist. In this study, we report a new family of proteins distantly related to outer kinetochore proteins Ndc80 and Nuf2. The family member in kinetoplastids, KKT-interacting protein 1 (KKIP1), associates with the kinetochore, and its depletion causes severe defects in karyokinesis, loss of individual chromosomes, and gross defects in spindle assembly or stability. Immunopurification of KKIP1 from stabilized kinetochores identifies six further components, which form part of a trypanosome outer kinetochore complex. These findings suggest that kinetochores in organisms such as kinetoplastids are built from a divergent, but not ancestrally distinct, set of components and that Ndc80/Nuf2-like proteins are universal in eukaryotic division.
动粒是将真核生物染色体与有丝分裂纺锤体相连以确保正确分离的多蛋白复合体。动粒组装模型在人类和酵母之间是保守的，并且几个组成部分的同源物在真核生物中广泛分布，但关键组成部分在一些谱系中不存在。最近在一种称为动基体的原生动物谱系中发现了非常规动粒，它们与模式生物没有明显的同源性，这表明可能存在不止一种真核生物染色体分离系统。在这项研究中，我们报告了一个与动粒外蛋白Ndc80和Nuf2远缘相关的新蛋白家族。动基体中的家族成员，动粒相互作用蛋白1（KKIP1），与动粒相关，其缺失会导致核分裂严重缺陷、个别染色体丢失以及纺锤体组装或稳定性的严重缺陷。从稳定的动粒中免疫纯化KKIP1可鉴定出另外六个组成部分，它们构成了锥虫动粒外复合体的一部分。这些发现表明，动基体等生物中的动粒是由一组不同但并非在进化上完全不同的组成部分构建而成，并且Ndc80/Nuf2样蛋白在真核生物分裂中是普遍存在的。
