Mana-Capelli Sebastian, Gräf Ralph, Larochelle Denis A
Department of Biology, Clark University, Worcester, MA 01610, USA.
Eukaryot Cell. 2009 Aug;8(8):1106-17. doi: 10.1128/EC.00025-09. Epub 2009 May 22.
Centrins are a family of proteins within the calcium-binding EF-hand superfamily. In addition to their archetypical role at the microtubule organizing center (MTOC), centrins have acquired multiple functionalities throughout the course of evolution. For example, centrins have been linked to different nuclear activities, including mRNA export and DNA repair. Dictyostelium discoideum centrin B is a divergent member of the centrin family. At the amino acid level, DdCenB shows 51% identity with its closest relative and only paralog, DdCenA. Phylogenetic analysis revealed that DdCenB and DdCenA form a well-supported monophyletic and divergent group within the centrin family of proteins. Interestingly, fluorescently tagged versions of DdCenB were not found at the centrosome (in whole cells or in isolated centrosomes). Instead, DdCenB localized to the nuclei of interphase cells. This localization disappeared as the cells entered mitosis, although Dictyostelium cells undergo a closed mitosis in which the nuclear envelope (NE) does not break down. DdCenB knockout cells exhibited aberrant nuclear architecture, characterized by enlarged and deformed nuclei and loss of proper centrosome-nucleus anchoring (observed as NE protrusions). At the centrosome, loss of DdCenB resulted in defects in the organization and morphology of the MTOC and supernumerary centrosomes and centrosome-related bodies. The multiple defects that the loss of DdCenB generated at the centrosome can be explained by its atypical division cycle, transitioning into the NE as it divides at mitosis. On the basis of these findings, we propose that DdCenB is required at interphase to maintain proper nuclear architecture, and before delocalizing from the nucleus, DdCenB is part of the centrosome duplication machinery.
中心蛋白是钙结合EF手超家族中的一类蛋白质。除了在微管组织中心(MTOC)发挥其典型作用外,中心蛋白在进化过程中还获得了多种功能。例如,中心蛋白与不同的核活动有关,包括mRNA输出和DNA修复。盘基网柄菌中心蛋白B是中心蛋白家族中一个不同寻常的成员。在氨基酸水平上,盘基网柄菌中心蛋白B与其最接近的亲属且唯一的旁系同源物盘基网柄菌中心蛋白A的同源性为51%。系统发育分析表明,盘基网柄菌中心蛋白B和盘基网柄菌中心蛋白A在中心蛋白家族中形成了一个得到充分支持的单系且不同寻常的类群。有趣的是,在中心体(在完整细胞或分离的中心体中)未发现荧光标记的盘基网柄菌中心蛋白B版本。相反,盘基网柄菌中心蛋白B定位于间期细胞的细胞核。随着细胞进入有丝分裂,这种定位消失,尽管盘基网柄菌细胞进行的是封闭有丝分裂,其中核膜(NE)不会解体。盘基网柄菌中心蛋白B基因敲除细胞表现出异常的核结构,其特征是细胞核增大和变形,以及失去适当的中心体 - 细胞核锚定(表现为核膜突出)。在中心体,盘基网柄菌中心蛋白B的缺失导致微管组织中心的组织和形态缺陷以及多余的中心体和与中心体相关的体。盘基网柄菌中心蛋白B缺失在中心体产生的多种缺陷可以用其非典型的分裂周期来解释,即在有丝分裂时分裂时过渡到核膜。基于这些发现,我们提出盘基网柄菌中心蛋白B在间期是维持适当核结构所必需的,并且在从细胞核中脱离之前,盘基网柄菌中心蛋白B是中心体复制机制的一部分。