PLK4 is a microtubule-associated protein that self-assembles promoting <i>de novo</i> MTOC formation

Abstract

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 <i>de novo</i> How centrosomes form <i>de novo</i> 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 <i>Xenopus</i> egg extracts, where PLK4 can induce <i>de novo</i> MTOC formation ( Eckerdt et al., 2011; Zitouni et al., 2016). Surprisingly, we observe that <i>in vitro</i>, PLK4 can self-assemble into condensates that recruit α- and β-tubulins. In <i>Xenopus</i> extracts, PLK4 assemblies additionally recruit STIL, a substrate of PLK4, and the microtubule nucleator γ-tubulin, forming acentriolar MTOCs <i>de novo</i> 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.