How does the Pericentriolar Matrix function in Centrosome Biology? (360G-Wellcome-209194_Z_17_Z)

Centrosomes are the major microtubule organising centres in many animal cells. They form when centrioles assemble an electron dense matrix of pericentriolar material (PCM) around themselves. Several hundred proteins are concentrated in the PCM, including many cell-cycle regulators and cell signalling molecules, and centrosomes function as important coordination centres within the cell. The underlying principles that allow centrioles to recruit and organise the many proteins required to form a functional centrosome are largely mysterious. Recent studies from our laboratories have identified a surprisingly simple pathway of mitotic centrosome assembly that is conserved in flies and worms. The centriole and PCM protein Spd-2/SPD-2 recruits the mitotic kinase Polo/PLK1 and the large coiled-coil protein Cnn/SPD-5 around the mother centriole. Polo/Plk1 then phosphorylates Cnn/SPD-5, allowing it to assemble into a micron-scale structure that recruits other PCM proteins. Our studies suggest that Cnn/SPD-5 molecules phase-separate into a biomolecular condensate that functions as a "scaffold" that then recruits the many "clients" necessary for centrosome function. Our goal is to understand at the atomic level the nature of the interactions that drive the assembly of the mitotic centrosomal-scaffold, and, by comparting the two different model systems, to describe a conserved pathway for centrosome assembly.