Phase Transitioning the Centrosome into a Microtubule Nucleator

Abstract

Centrosomes are self-assembling, micron-scale, nonmembrane bound organelles that nucleate microtubules (MTs) and organize the microtubule cytoskeleton of the cell. They orchestrate critical cellular processes such as ciliary-based motility, vesicle trafficking, and cell division. Much is known about the role of the centrosome in these contexts, but we have a less comprehensive understanding of how the centrosome assembles and generates microtubules. Studies over the past 10 years have fundamentally shifted our view of these processes. Subdiffraction imaging has probed the amorphous haze of material surrounding the core of the centrosome revealing a complex, hierarchically organized structure whose composition and size changes profoundly during the transition from interphase to mitosis. New biophysical insights into protein phase transitions, where a diffuse protein spontaneously separates into a locally concentrated, nonmembrane bounded compartment, have provided a fresh perspective into how the centrosome might rapidly condense from diffuse cytoplasmic components. In this Perspective, we focus on recent findings that identify several centrosomal proteins that undergo phase transitions. We discuss how to reconcile these results with the current model of the underlying organization of proteins in the centrosome. Furthermore, we reflect on how these findings impact our understanding of how the centrosome undergoes self-assembly and promotes MT nucleation.

Overexpression of the microtubule-binding protein CLIP-170 induces a +TIP network superstructure consistent with a biomolecular condensate

“…are dynamic structures that spontaneously form when interactions between groups of weakly-binding biopolymers (protein and sometimes RNA or DNA) cause them to phaseseparate from surrounding cytoplasm or nucleoplasm (21)(22)(23)(24). Cytosolic examples include P-bodies, which regulate mRNA turnover (25,26), Wnt signalosomes, which help to transduce Wnt signaling (27)(28)(29), and the pericentriolar material/matrix, which regulates MT nucleation at the centrosome (30,31). In the nucleus, Cajal bodies regulate RNA-related metabolism (32), and PML bodies regulate nuclear functions (33).…”

Moonlighting in Mitosis: Analysis of the Mitotic Functions of Transcription and Splicing Factors

“…Recent work has provided some clues on how proteins without direct centrosome-specific functions can concentrate in this organelle. It has been suggested that centrosome assembly is facilitated by the ability of several centrosomal proteins to undergo liquid-liquid phase transition and form liquid-like droplets that concentrate cytoplasmic components and then fuse to form the PCM around the centrioles [84]. These droplets may include cytoplasmic proteins that will become spurious centrosome components.…”

Plk4 triggers autonomous de novo centriole biogenesis and maturation

“…The change in the kinetics of de novo centriole assembly in response to Plk4 concentration allied to the current body of knowledge in the centrosome field, collectively suggest that centriole formation is critically regulated by timely concentration of centrosomal molecules in one single place (Rale et al, 2018; Takao et al, 2019). But what initiates the concentration of these centrosomal molecules?…”