A mature centrosome is composed of a pair of centrioles surrounded by pericentriolar material (PCM). Centrosomal dysfunction has been frequently linked to numerous serious diseases and disorders, including cancer, dysplasia, brain developmental disorders, degeneration, and others ( Bornens, 2012 Conduit et al., 2015 Nigg and Holland, 2018 Nigg and Raff, 2009). Collectively, our results demonstrate that PLK4-regulated NEDD1 facilitates initiation of the cartwheel assembly and of daughter centriole biogenesis in mammals.Ĭentrosomes, the main microtubule-organizing centers, are responsible for organizing the interphase microtubule cytoskeleton and the mitotic spindle, which are crucial for both intracellular material transport and chromosome segregation during cell division in vertebrates. Overexpression of phosphomimicking NEDD1 mutant S325E promoted cartwheel assembly and daughter centriole biogenesis initiations, whereas overexpression of nonphosphorylatable NEDD1 mutant S325A abolished the initiations. We found that PLK4-mediated phosphorylation of NEDD1 at its S325 amino acid residue directly promotes both NEDD1 binding to SAS-6 and recruiting SAS-6 to the centrosome. Here, we show that cartwheel assembly followed by daughter centriole biogenesis is initiated on the NEDD1-containing layer of the pericentriolar material (PCM) by the recruitment of SAS-6 to the mother centriole under the regulation of PLK4. However, although much of this process is understood, how centrosome duplication is initiated remains unclear. Centrosome duplication occurs under strict spatiotemporal regulation once per cell cycle, and it begins with cartwheel assembly and daughter centriole biogenesis at the lateral sites of the mother centrioles.
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