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Transiently formed nucleus-to-cilium microtubule arrays mediate senescence initiation in a KIFC3-dependent manner

Author

Listed:
  • Jielu Hao Robichaud

    (Mayo Clinic)

  • Yingyi Zhang

    (Mayo Clinic)

  • Chuan Chen

    (Mayo Clinic)

  • Kai He

    (Mayo Clinic)

  • Yan Huang

    (Mayo Clinic)

  • Xu Zhang

    (Mayo Clinic
    Mayo Clinic)

  • Xiaobo Sun

    (Mayo Clinic)

  • Xiaoyu Ma

    (Mayo Clinic)

  • Gary Hardiman

    (Institute for Global Food Security (IGFS), Queen’s University Belfast)

  • Ciaran G. Morrison

    (School of Biological and Chemical Sciences, University of Galway)

  • Zheng Dong

    (Medical College of Georgia at Augusta University
    Charlie Norwood VA Medical Center)

  • Nathan K. LeBrasseur

    (Mayo Clinic
    Mayo Clinic
    Mayo Clinic)

  • Kun Ling

    (Mayo Clinic)

  • Jinghua Hu

    (Mayo Clinic
    Mayo Clinic
    Mayo Clinic)

Abstract

Despite the importance of cellular senescence in human health, how damaged cells undergo senescence remains elusive. We have previously shown that promyelocytic leukemia nuclear body (PML-NBs) translocation of the ciliary FBF1 is essential for senescence induction in stressed cells. Here we discover that an early cellular event occurring in stressed cells is the transient assembly of stress-induced nucleus-to-cilium microtubule arrays (sinc-MTs). The sinc-MTs are distinguished by unusual polyglutamylation and unique polarity, with minus-ends nucleating near the nuclear envelope and plus-ends near the ciliary base. KIFC3, a minus-end-directed kinesin, is recruited to plus-ends of sinc-MTs and interacts with the centrosomal protein CENEXIN1. In damaged cells, CENEXIN1 co-translocates with FBF1 to PML-NBs. Deficiency of KIFC3 abolishes PML-NB translocation of FBF1 and CENEXIN1, as well as senescence initiation in damaged cells. Our study reveals that KIFC3-mediated nuclear transport of FBF1 along polyglutamylated sinc-MTs is a prerequisite for senescence induction in mammalian cells.

Suggested Citation

  • Jielu Hao Robichaud & Yingyi Zhang & Chuan Chen & Kai He & Yan Huang & Xu Zhang & Xiaobo Sun & Xiaoyu Ma & Gary Hardiman & Ciaran G. Morrison & Zheng Dong & Nathan K. LeBrasseur & Kun Ling & Jinghua H, 2024. "Transiently formed nucleus-to-cilium microtubule arrays mediate senescence initiation in a KIFC3-dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52363-w
    DOI: 10.1038/s41467-024-52363-w
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    References listed on IDEAS

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    1. Xiaoyu Ma & Yingyi Zhang & Yuanyuan Zhang & Xu Zhang & Yan Huang & Kai He & Chuan Chen & Jielu Hao & Debiao Zhao & Nathan K. LeBrasseur & James L. Kirkland & Eduardo N. Chini & Qing Wei & Kun Ling & J, 2023. "A stress-induced cilium-to-PML-NB route drives senescence initiation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Darren J. Baker & Tobias Wijshake & Tamar Tchkonia & Nathan K. LeBrasseur & Bennett G. Childs & Bart van de Sluis & James L. Kirkland & Jan M. van Deursen, 2011. "Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders," Nature, Nature, vol. 479(7372), pages 232-236, November.
    3. Kai He & Xiaoyu Ma & Tao Xu & Yan Li & Allen Hodge & Qing Zhang & Julia Torline & Yan Huang & Jian Zhao & Kun Ling & Jinghua Hu, 2018. "Axoneme polyglutamylation regulated by Joubert syndrome protein ARL13B controls ciliary targeting of signaling molecules," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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