Cell Cycle Regulation Laboratory, Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, 2780-156, Portugal
Cell Cycle Regulation Laboratory, Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, 2780-156, Portugal.
J Cell Sci. 2018 Nov 9;132(4):jcs219501. doi: 10.1242/jcs.219501.
The centrosome is an important microtubule-organising centre (MTOC) in animal cells. It consists of two barrel-shaped structures, the centrioles, surrounded by the pericentriolar material (PCM), which nucleates microtubules. Centrosomes can form close to an existing structure (canonical duplication) or How centrosomes form is not known. The master driver of centrosome biogenesis, PLK4, is critical for the recruitment of several centriole components. Here, we investigate the beginning of centrosome biogenesis, taking advantage of egg extracts, where PLK4 can induce MTOC formation ( Eckerdt et al., 2011; Zitouni et al., 2016). Surprisingly, we observe that , PLK4 can self-assemble into condensates that recruit α- and β-tubulins. In extracts, PLK4 assemblies additionally recruit STIL, a substrate of PLK4, and the microtubule nucleator γ-tubulin, forming acentriolar MTOCs The assembly of these robust microtubule asters is independent of dynein, similar to what is found for centrosomes. We suggest a new mechanism of action for PLK4, where it forms a self-organising catalytic scaffold that recruits centriole components, PCM factors and α- and β-tubulins, leading to MTOC formation.This article has an associated First Person interview with the first author of the paper.
中心体是动物细胞中重要的微管组织中心（MTOC）。它由两个桶状结构组成，即中心粒，被中心粒周围物质（PCM）包围，PCM 可以核生成微管。中心体可以在现有结构附近形成（经典复制），也可以形成。目前尚不清楚中心体如何形成。中心体生物发生的主要驱动蛋白 PLK4 对于几种中心粒成分的募集至关重要。在这里，我们利用 PLK4 可以诱导 MTOC 形成的卵提取物来研究中心体生物发生的开始（Eckerdt 等人，2011 年；Zitouni 等人，2016 年）。令人惊讶的是，我们观察到 PLK4 可以自组装成含有α-和β-微管蛋白的凝聚物。在提取物中，PLK4 组装物还募集 PLK4 的底物 STIL 和微管核形成因子γ-微管蛋白，形成无中心粒的 MTOC。这些坚固的微管星状体的组装不依赖于动力蛋白，与中心体的情况类似。我们提出了一种 PLK4 的新作用机制，即它形成自我组织的催化支架，募集中心粒成分、PCM 因子和α-和β-微管蛋白，从而导致 MTOC 的形成。本文附有该论文第一作者的第一人称访谈。
