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Phosphorylation remodels the mitotic centrosome matrix to generate bipartite γ-tubulin complex docking sites - PubMed

3 hours ago
  • #phosphorylation
  • #mitotic centrosome
  • #microtubule nucleation
  • Phosphorylation at centrosomes during mitotic entry remodels matrix proteins like CDK5RAP2 to create docking sites for γ-tubulin complexes (γTuCs), which nucleate microtubules for spindle assembly.
  • Using C. elegans SPD-5 as a model, two regions (PRGB1 and PRGB2) are identified, each sufficient for PLK1 phosphorylation-regulated γTuC binding, with defined key phosphosites and mechanisms of autoinhibition.
  • PRGB2 is dimeric and requires γTuCs containing MZT-1 for binding, whereas PRGB1 is monomeric and MZT-1-independent; phosphorylation induces a conformational change enabling MZT-1-dependent PRGB2 engagement, relieving PRGB1 inhibition.
  • This multistep mechanism ensures robust spindle assembly by spatially and temporally restricting microtubule nucleation.