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<p>Mitotic centrosome maturation requires Polo/PLK1-dependent expansion of the pericentriolar material (PCM). In <i>Drosophila</i>, Centrosomin (Cnn) assembles a scaffold around mitotic centrioles through interactions between its PReM and CM2 domains. Here, we show that PReM adopts an autoinhibited helical hairpin conformation that prevents CM2 binding. Polo/PLK1 phosphorylation relieves this autoinhibition, enabling scaffold assembly, whereas phospho-blocking mutations disrupt PReM–CM2 binding in vitro and Cnn scaffold assembly in vivo. Potential functionally analogous domains have been identified in the human and <i>C. elegans</i> Cnn homologues CDK5RAP2 and SPD-5. We find that the human protein appears to share a structurally similar mechanism for scaffold assembly, but the worm protein does not. Consistent with this, deletion of these domains alters the dynamics of Cnn condensates in vitro, but has little effect on SPD-5 condensate dynamics. We conclude that Polo/PLK1 promotes mitotic centrosome assembly, at least in part, by relieving autoinhibitory intramolecular interactions.</p>

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Polo/PLK1 phosphorylation relieves Centrosomin/Cnn autoinhibition to promote centrosome scaffold assembly

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月30日

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  • Nada Mohamad,
  • Siu-Shing Wong,
  • Anupa Majumdar,
  • Alan Wainman,
  • Ingelise Holland-Kaye,
  • Lars Hubatsch,
  • Zsofia Novak,
  • Andrey Pozniakovsky,
  • Martine Ruer-Gruss,
  • Andreas F M Haensele,
  • Anna Caballe,
  • Steven Johnson,
  • Susan M Lea,
  • Anthony A Hyman,
  • Jordan W Raff

摘要

Mitotic centrosome maturation requires Polo/PLK1-dependent expansion of the pericentriolar material (PCM). In Drosophila, Centrosomin (Cnn) assembles a scaffold around mitotic centrioles through interactions between its PReM and CM2 domains. Here, we show that PReM adopts an autoinhibited helical hairpin conformation that prevents CM2 binding. Polo/PLK1 phosphorylation relieves this autoinhibition, enabling scaffold assembly, whereas phospho-blocking mutations disrupt PReM–CM2 binding in vitro and Cnn scaffold assembly in vivo. Potential functionally analogous domains have been identified in the human and C. elegans Cnn homologues CDK5RAP2 and SPD-5. We find that the human protein appears to share a structurally similar mechanism for scaffold assembly, but the worm protein does not. Consistent with this, deletion of these domains alters the dynamics of Cnn condensates in vitro, but has little effect on SPD-5 condensate dynamics. We conclude that Polo/PLK1 promotes mitotic centrosome assembly, at least in part, by relieving autoinhibitory intramolecular interactions.