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<p>During cell division, the nuclear mitotic apparatus protein (NuMA) orchestrates the focusing of microtubule minus-ends in spindle poles and cortical force generation on astral microtubules by interacting with dynein motors, microtubules and other cellular factors. Here we used in vitro reconstitution, cryo-electron microscopy and live-cell imaging to understand the mechanism and regulation of NuMA. We determined the structure of the processive dynein–dynactin–NuMA complex (DDN) and showed that the NuMA N terminus drives dynein motility in vitro and facilitates dynein-mediated transport in live cells. The C terminus of NuMA directly binds and suppresses the dynamics of the microtubule minus-end. Full-length NuMA is autoinhibited for its interactions with dynein and microtubules, whereas mitotically phosphorylated NuMA activates dynein in vitro and interphase cells. Together with dynein, activated full-length NuMA focuses microtubule minus-ends into aster-like structures. These results provide critical insights into the activation of NuMA and dynein for their mitotic functions.</p><p></p>

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Activation and regulation of the dynein–dynactin–NuMA complex

  • 期刊论文

  • 发表日期：

    2026年3月16日

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  • Merve Aslan,
  • Ennio A. d’Amico,
  • Nathan H. Cho,
  • Aryan Taheri,
  • Juan M. Perez-Bertoldi,
  • Yuanchang Zhao,
  • Xinyue Zhong,
  • Madeline Blaauw,
  • Andrew P. Carter,
  • Sophie Dumont,
  • Ahmet Yildiz

摘要

During cell division, the nuclear mitotic apparatus protein (NuMA) orchestrates the focusing of microtubule minus-ends in spindle poles and cortical force generation on astral microtubules by interacting with dynein motors, microtubules and other cellular factors. Here we used in vitro reconstitution, cryo-electron microscopy and live-cell imaging to understand the mechanism and regulation of NuMA. We determined the structure of the processive dynein–dynactin–NuMA complex (DDN) and showed that the NuMA N terminus drives dynein motility in vitro and facilitates dynein-mediated transport in live cells. The C terminus of NuMA directly binds and suppresses the dynamics of the microtubule minus-end. Full-length NuMA is autoinhibited for its interactions with dynein and microtubules, whereas mitotically phosphorylated NuMA activates dynein in vitro and interphase cells. Together with dynein, activated full-length NuMA focuses microtubule minus-ends into aster-like structures. These results provide critical insights into the activation of NuMA and dynein for their mitotic functions.