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线虫纤毛基部的无中心体中心粒。

An acentriolar centrosome at the C. elegans ciliary base.

机构信息

Max Perutz Labs, University of Vienna, Vienna Biocenter (VBC), Dr Bohr-Gasse 9, A-1030 Vienna, Austria; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna.

Max Perutz Labs, University of Vienna, Vienna Biocenter (VBC), Dr Bohr-Gasse 9, A-1030 Vienna, Austria.

出版信息

Curr Biol. 2021 Jun 7;31(11):2418-2428.e8. doi: 10.1016/j.cub.2021.03.023. Epub 2021 Apr 1.

Abstract

In animal cells, the functions of the microtubule cytoskeleton are coordinated by centriole-based centrosomes via γ-tubulin complexes embedded in the pericentriolar material or PCM. PCM assembly has been best studied in the context of mitosis, where centriolar SPD-2 recruits PLK-1, which in turn phosphorylates key scaffolding components like SPD-5 and CNN to promote expansion of the PCM polymer. To what extent these mechanisms apply to centrosomes in interphase or in differentiated cells remains unclear. Here, we examine a novel type of centrosome found at the ciliary base of C. elegans sensory neurons, which we show plays important roles in neuronal morphogenesis, cellular trafficking, and ciliogenesis. These centrosomes display similar dynamic behavior to canonical, mitotic centrosomes, with a stable PCM scaffold and dynamically localized client proteins. Unusually, however, they are not organized by centrioles, which degenerate early in terminal differentiation. Yet, PCM not only persists but continues to grow with key scaffolding proteins including SPD-5 expressed under control of the RFX transcription factor DAF-19. This assembly occurs in the absence of the mitotic regulators SPD-2, AIR-1 and PLK-1, but requires tethering by PCMD-1, a protein which also plays a role in the initial, interphase recruitment of PCM in early embryos. These results argue for distinct mechanisms for mitotic and non-mitotic PCM assembly, with only the former requiring PLK-1 phosphorylation to drive rapid expansion of the scaffold polymer.

摘要

在动物细胞中,微管细胞骨架的功能通过中心体上的中心粒来协调,中心体通过嵌入中心粒周围物质(PCM)中的 γ-微管蛋白复合物来发挥作用。PCM 的组装在有丝分裂的背景下研究得最好,在有丝分裂中,中心体 SPD-2 招募 PLK-1,PLK-1 反过来磷酸化关键支架成分,如 SPD-5 和 CNN,以促进 PCM 聚合物的扩展。这些机制在有丝分裂期或分化细胞中的中心体中适用到何种程度尚不清楚。在这里,我们研究了在秀丽隐杆线虫感觉神经元的纤毛基部发现的一种新型中心体,我们发现它在神经元形态发生、细胞运输和纤毛发生中发挥重要作用。这些中心体表现出与经典的有丝分裂中心体相似的动态行为,具有稳定的 PCM 支架和动态定位的客户蛋白。然而,不同寻常的是,它们不是由中心粒组织的,中心粒在终末分化的早期就退化了。然而,PCM 不仅持续存在,而且继续生长,关键的支架蛋白包括 SPD-5 在 RFX 转录因子 DAF-19 的控制下表达。这种组装发生在没有有丝分裂调节剂 SPD-2、AIR-1 和 PLK-1 的情况下,但需要通过 PCMD-1 来固定,PCMD-1 蛋白在早期胚胎中 PCM 的初始、有丝分裂招募中也发挥作用。这些结果表明有丝分裂和非有丝分裂 PCM 组装有不同的机制,只有前者需要 PLK-1 磷酸化来驱动支架聚合物的快速扩展。

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