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NuMA regulates mitotic spindle assembly, structural dynamics and function via phase separation

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  • Mengjie Sun

    (College of Life Sciences, Peking University)

  • Mingkang Jia

    (College of Life Sciences, Peking University)

  • He Ren

    (College of Life Sciences, Peking University)

  • Biying Yang

    (College of Life Sciences, Peking University)

  • Wangfei Chi

    (College of Life Sciences, Peking University)

  • Guangwei Xin

    (College of Life Sciences, Peking University)

  • Qing Jiang

    (College of Life Sciences, Peking University)

  • Chuanmao Zhang

    (College of Life Sciences, Peking University)

Abstract

A functional mitotic spindle is essential for accurate chromosome congression and segregation during cell proliferation; however, the underlying mechanisms of its assembly remain unclear. Here we show that NuMA regulates this assembly process via phase separation regulated by Aurora A. NuMA undergoes liquid-liquid phase separation during mitotic entry and KifC1 facilitates NuMA condensates concentrating on spindle poles. Phase separation of NuMA is mediated by its C-terminus, whereas its dynein-dynactin binding motif also facilitates this process. Phase-separated NuMA droplets concentrate tubulins, bind microtubules, and enrich crucial regulators, including Kif2A, at the spindle poles, which then depolymerizes spindle microtubules and promotes poleward spindle microtubule flux for spindle assembly and structural dynamics. In this work, we show that NuMA orchestrates mitotic spindle assembly, structural dynamics and function via liquid-liquid phase separation regulated by Aurora A phosphorylation.

Suggested Citation

  • Mengjie Sun & Mingkang Jia & He Ren & Biying Yang & Wangfei Chi & Guangwei Xin & Qing Jiang & Chuanmao Zhang, 2021. "NuMA regulates mitotic spindle assembly, structural dynamics and function via phase separation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27528-6
    DOI: 10.1038/s41467-021-27528-6
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    Cited by:

    1. Anna Rodina & Chao Xu & Chander S. Digwal & Suhasini Joshi & Yogita Patel & Anand R. Santhaseela & Sadik Bay & Swathi Merugu & Aftab Alam & Pengrong Yan & Chenghua Yang & Tanaya Roychowdhury & Palak P, 2023. "Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation," Nature Communications, Nature, vol. 14(1), pages 1-26, December.
    2. Maruša Ramšak & Dominique A. Ramirez & Loren E. Hough & Michael R. Shirts & Sara Vidmar & Kristina Eleršič Filipič & Gregor Anderluh & Roman Jerala, 2023. "Programmable de novo designed coiled coil-mediated phase separation in mammalian cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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