Aurora A Regulates Nuclear Envelope Formation during Cell Division

Eukaryotic cells face a critical challenge each time they divide: they must equally duplicate and separate their chromosomes and then rebuild the nuclear envelope around the split genetic material. Failure in this process can lead to misshapen or disorganized nuclei, characteristics often observed in cancer and age-related diseases. A collaborative study from the Indian Institute of Science and Université Paris-Saclay has elucidated the role of a key enzyme, Aurora A, in facilitating this complex task.

During mitosis, spindle poles or centrosomes enlarge to create microtubule tracks that pull chromosomes apart. After chromosome separation is complete, these spindle poles need to disassemble to enable the nuclear envelope to reform around the chromosomes. According to Sachin Kotak, lead author of the study published in The EMBO Journal, the reason for spindle poles disassembling, their material properties, and their relevance remained unclear until this study. 

The research revealed that Aurora A is essential for timely disassembly of spindle poles. When Aurora A is absent or inhibited, spindle poles become "sticky," causing chromosomes to bend irregularly and resulting in distorted nuclei.

A protein called NuMA, crucial for organizing spindle poles, behaves dynamically during this process. Normally, NuMA aggregates at spindle poles during mitosis but disperses as cells finish dividing. Aurora A maintains NuMA in a liquid-like, dynamic state, allowing it to move fluidly. Without Aurora A’s activity, NuMA hardens and clumps at the poles, disrupting normal spindle disassembly. Using advanced imaging, the team identified how Aurora A phosphorylates NuMA to prevent this hardening and pinpointed specific regions and amino acids responsible for NuMA’s transition between liquid and solid states.

Kotak emphasized that the study shows the importance of proteins’ material states—whether they act like liquids or solids—beyond merely their presence. This regulation by Aurora A ensures smooth dissolution of spindle poles, allowing proper nuclear envelope formation and genome encapsulation.

One challenge in studying Aurora A was its role early in mitosis. Complete removal halts mitosis, preventing study of later phases. “One of the cool things we have done in this work is make a tool by which we can destroy Aurora A when cells exit mitosis,” says Kotak. This allowed the team to show that the enzyme’s later role in nuclei formation is distinct from its well-known earlier function in spindle assembly.

Overall, the findings highlight the elegant choreography involved in mitosis and open up the possibility of targeting these protein states for therapeutic applications.