Transiently formed nucleus-to-cilium microtubule arrays mediate senescence initiation in a KIFC3-dependent manner
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.
Authors
- Xiaoyu Ma (ORCID: https://orcid.org/0000-0002-9347-3565)
- Nathan K. LeBrasseur (ORCID: https://orcid.org/0000-0002-2002-0418)
- Gary Hardiman (ORCID: https://orcid.org/0000-0003-4558-0400)
- Ciaran G. Morrison (ORCID: https://orcid.org/0000-0003-2401-7029)
- Zheng Dong (ORCID: https://orcid.org/0000-0003-3538-8095)
- Jinghua Hu (ORCID: https://orcid.org/0000-0001-9635-9779)
- Kun Ling (ORCID: https://orcid.org/0000-0002-2388-5492)
- Kai He (ORCID: https://orcid.org/0000-0001-6405-8330)
- Jielu Hao Robichaud
- Chuan Chen (ORCID: https://orcid.org/0000-0002-0694-0867)
- Xu Zhang (ORCID: https://orcid.org/0000-0002-9784-0481)
- Yingyi Zhang (ORCID: https://orcid.org/0000-0003-1020-7964)
- Yan Huang (ORCID: https://orcid.org/0000-0002-1045-4044)
- Xiaobo Sun
Institutions
- Queen's University Belfast (GB)
- Mayo Clinic (US)
- Ollscoil na Gaillimhe – University of Galway (IE)
- Augusta University (US)
- Charlie Norwood VA Medical Center (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic in Florida (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-12
- DOI
- https://doi.org/10.1038/s41467-024-52363-w
- Citations
- 7
- Primary Topic
- Microtubule and mitosis dynamics
- Type
- article
- Field-Weighted Citation Impact
- 2.28
Funders
- U.S. Department of Defense
- Foundation for the National Institutes of Health
- American Society of Nephrology
- ASN Foundation for Kidney Research