Adapting plasma membrane for mitotic cell rounding through Aurora A phosphorylation of numb

  • J Cell Biol. 2025 Dec 1;224(12):e202412005. doi: 10.1083/jcb.202412005.
Yanyan Li  #  1  2  3  4 ,  Ke Liu  #  1  3  4  5 ,  Xian Lin  #  6 ,  Zhihao Ding  #  1 ,  Haiyan Sun  1 ,  Xiangyun Liao  1 ,  Binghua Cheng  1  2  3  4 ,  Wenli Shi  1  7 ,  Junde Xu  1 ,  Jiaming Liang  1  2  3  4 ,  Zeyu Zhou  1  8 ,  Wenjie Zhou  1  8 ,  Hui Tian  1  8 ,  Long Meng  1  3  4 ,  Guangyong Chen  1 ,  Ximing Shao  1  3  4  5 ,  Hongchang Li  1  3  4  5
Affiliations
  • 1. Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • 2. University of Chinese Academy of Sciences , Beijing, China.
  • 3. Key Laboratory of Biomedical Imaging Science and System, Chinese Academy of Sciences, Shenzhen, China.
  • 4. State Key Laboratory of Biomedical Imaging Science and System , Shenzhen, China.
  • 5. Sino-Euro Center of Biomedicine and Health , Shenzhen, China.
  • 6. Department of Pathology, Tianjin Medical University General Hospital, Tianjin, China.
  • 7. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Caserta, Italy.
  • 8. Southern University of Science and Technology , Shenzhen, China.
  • # Contributed equally.
PMID: 41212116 DOI: 10.1083/jcb.202412005
Abstract

Cell rounding during Mitosis necessitates adaptive remodeling of plasma membrane and cortical Cytoskeleton. However, the underlying mechanisms remain poorly elucidated. Here, we have identified Numb phosphorylation as a pivotal mechanism in the membrane-cytoskeleton remodeling associated with mitotic cell rounding. Upon mitotic entry, Aurora A phosphorylates Numb, leading to the dissociation of Numb from plasma membrane. This is crucial for proper plasma membrane retraction, since overexpression of a non-phosphorylatable mutant or a constitutively membrane-bound variant of Numb dramatically disrupts mitotic plasma membrane retraction. Mechanistically, releasing Numb from the plasma membrane enhances the Myosin I-mediated membrane-to-cortex adhesion, thereby facilitating the plasma membrane retraction accompanied with cytoskeletal withdrawal. Further analysis showed that compromised plasma membrane retraction confines mitotic cell rounding and consequently leads to spindle orientation defects. Thus, our study elucidates a phosphorylation-mediated mechanism underlying plasma membrane retraction and underscores the functional importance of this process in the context of mitotic cell rounding.

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