Centrioles generate two scaffolds with distinct biophysical properties to build mitotic centrosomes

Abstract

Mitotic centrosomes form when centrioles recruit large amounts of pericentriolar material (PCM) around themselves. The PCM comprises hundreds of proteins, yet it can assemble and disassemble within minutes, leading to much debate about its physical nature. Here we show thatDrosophilaSpd-2 fluxes out from centrioles, recruiting Polo and Aurora A to catalyse the assembly of a solid-like Cnn-scaffold and a more liquid-like TACC-scaffold, respectively. Both scaffolds can assemble and recruit PCM proteins independently, but both are required for proper centrosome assembly, with the Cnn-scaffold providing mechanical strength, and the TACC-scaffold locally concentrating centriole and centrosome proteins. Recruiting Spd-2, but not Cnn or TACC, to the surface of synthetic beads injected into early embryos reconstitutes several aspects of mitotic centrosome assembly on the bead surface, and this depends on the ability of Spd-2 to recruit Polo and AurA. Thus, Spd-2 molecules flux out from the centriole recruiting Polo and AurA to promote the assembly of two scaffolds with distinct properties to support mitotic centrosome assembly in flies.

Structural characterization and inhibition of the interaction between ch-TOG and TACC3

“…Instead, the phenotype points to a recently described property of TACC3 at spindle poles. First in Drosophila spindles, the PCM is templated by a cnn-containing structure with a more liquid-like D-TACC region associated with it (Wong et al, 2024). Second in C. elegans oocyte meiotic spindles, XMAP215/ZYG-9 and TACC/TAC-1 act at multiple times during assembly to promote spindle pole integrity and stability (Harvey et al, 2023).…”

“…In agreement with this, evidence from mammalian oocytes – where the spindle is formed without centrosomes – is that TACC3 forms a liquid-like domain at spindle poles (Fu et al, 2013; So et al, 2019). Finally, back to Drosophila , recent work indicates that D-TACC forms a liquid-like scaffold in the pericentriolar material (PCM) and not at the centrosome itself (Wong et al, 2024).…”