eLife (Jul 2022)

Self-assembly of pericentriolar material in interphase cells lacking centrioles

  • 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,
  • Florian Berger,
  • Anna Akhmanova

DOI
https://doi.org/10.7554/eLife.77892
Journal volume & issue
Vol. 11

Abstract

Read online

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 PCM binding to centrioles, PCM self-association and dynein-mediated PCM transport, but the self-assembly properties of PCM components in interphase cells are poorly understood. Here, we used experiments and modeling to study centriole-independent features of interphase PCM assembly. We showed that when centrioles are lost due to PLK4 depletion or inhibition, dynein-based transport and self-clustering of PCM proteins are sufficient to form a single compact MTOC, which generates a dense radial microtubule array. Interphase self-assembly of PCM components depends on γ-tubulin, pericentrin, CDK5RAP2 and ninein, but not NEDD1, CEP152, or CEP192. Formation of a compact acentriolar MTOC is inhibited by AKAP450-dependent PCM recruitment to the Golgi or by randomly organized CAMSAP2-stabilized microtubules, which keep PCM mobile and prevent its coalescence. Linking of CAMSAP2 to a minus-end-directed motor leads to the formation of an MTOC, but MTOC compaction requires cooperation with pericentrin-containing self-clustering PCM. Our data reveal that interphase PCM contains a set of components that can self-assemble into a compact structure and organize microtubules, but PCM self-organization is sensitive to motor- and microtubule-based rearrangement.

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