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Centriole-independent centrosome assembly in interphase mammalian cells

By Fangrui Chen, Jingchao Wu, Malina K. Iwanski, Daphne Jurriens, Arianna Sandron, Milena Pasolli, Gianmarco Puma, Jannes Z. Kromhout, Chao Yang, Wilco Nijenhuis, Lukas C. Kapitein, Anna Akhmanova

Posted 23 Aug 2021
bioRxiv DOI: 10.1101/2021.08.22.457259

The major microtubule-organizing center (MTOC) in animal cells, the centrosome, comprises a pair of centrioles surrounded by pericentriolar material (PCM), which nucleates and anchors microtubules. Centrosome assembly depends on the interactions of PCM with centrioles, PCM self-association and dynein-mediated transport. Here, we show that if centrioles are lost due to PLK4 depletion or inhibition, PCM still forms a single centrally located MTOC when non-centrosomal microtubule minus end organization pathways are disabled. Acentriolar MTOC assembly depends on dynein-driven coalescence of PCM clusters with attached microtubule minus ends and requires {gamma}-tubulin, pericentrin, CDK5RAP2 and ninein, but not NEDD1, CEP152 or CEP192. PCM self-assembly is inhibited by AKAP450-dependent PCM recruitment to the Golgi and by CAMSAP2-mediated microtubule minus end stabilization. However, if CAMSAP2 is linked to a minus-end-directed motor, a single MTOC containing PCM components can still form, and its organization depends on the presence of pericentrin. Our results reveal that the formation of a single central MTOC in interphase mammalian cells is not strictly centriole dependent but can be driven by self-organization of PCM and microtubule minus ends.

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