<p>Accurate segregation of mitotic chromosomes requires pre-anaphase alignment driven by microtubule-based motor proteins. Tubulin detyrosination is essential to guide CENP-E-driven chromosome congression in mitosis. However, the mechanisms of action and physiochemical properties of the detyrosinases for decoding CENP-E motility remain elusive. Here we show that microtubule-associated tyrosine carboxypeptidase (MATCAP) undergoes intrinsically disordered region (IDR)-dependent&#xa0;liquid-liquid phase separation (LLPS) on microtubules to constitute the tubulin detyrosination machinery. These biomolecular condensates selectively enrich tubulin and CENP-E, thereby stabilizing kinetochore-microtubule attachments. Real-time imaging of cells expressing LLPS-deficient MATCAP mutants reveals the importance of MATCAP LLPS dynamics in mitotic chromosome alignment. Mechanistically, phase separation of MATCAP spatiotemporally couples tubulin detyrosination with CENP-E motility to ensure a robust chromosome alignment during mitosis. These findings delineate a signaling cascade that integrates phase separation and tubulin detyrosination with mitotic progression for the&#xa0;maintenance of genomic stability.</p>

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Condensation of MATCAP promotes CENP-E-dependent chromosome congression in mitosis

  • Tongtong Yang,
  • Wenping Hu,
  • Panpan Xu,
  • Huanyu Li,
  • Yaqian Zhang,
  • Fangyuan Xiong,
  • Yunze Li,
  • Chao Xu,
  • Ke Ruan,
  • Zhonghuai Hou,
  • Zhikai Wang,
  • Liangyu Zhang,
  • Xuebiao Yao,
  • Shengqi Xiang,
  • Kai Jiang,
  • Xing Liu

摘要

Accurate segregation of mitotic chromosomes requires pre-anaphase alignment driven by microtubule-based motor proteins. Tubulin detyrosination is essential to guide CENP-E-driven chromosome congression in mitosis. However, the mechanisms of action and physiochemical properties of the detyrosinases for decoding CENP-E motility remain elusive. Here we show that microtubule-associated tyrosine carboxypeptidase (MATCAP) undergoes intrinsically disordered region (IDR)-dependent liquid-liquid phase separation (LLPS) on microtubules to constitute the tubulin detyrosination machinery. These biomolecular condensates selectively enrich tubulin and CENP-E, thereby stabilizing kinetochore-microtubule attachments. Real-time imaging of cells expressing LLPS-deficient MATCAP mutants reveals the importance of MATCAP LLPS dynamics in mitotic chromosome alignment. Mechanistically, phase separation of MATCAP spatiotemporally couples tubulin detyrosination with CENP-E motility to ensure a robust chromosome alignment during mitosis. These findings delineate a signaling cascade that integrates phase separation and tubulin detyrosination with mitotic progression for the maintenance of genomic stability.