Rajeevan Ashwathi, Olakkal Vignesh, Balakrishnan Madhumitha, Chakrabarty Dwaipayan, Charon François, Noordermeer Daan, Kotak Sachin
Department of Microbiology and Cell Biology (MCB), Indian Institute of Science (IISc), 560012, Bangalore, India.
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France.
EMBO J. 2025 Sep 12. doi: 10.1038/s44318-025-00564-4.
Animal cells dismantle their nuclear envelope (NE) at the beginning and reconstruct it at the end of mitosis. This process is closely coordinated with spindle pole organization: poles enlarge at mitotic onset and reduce in size as mitosis concludes. The significance of this coordination remains unknown. Here, we demonstrate that Aurora A maintains a pole-localized protein NuMA in a dynamic state during anaphase. Without Aurora A activity, NuMA shifts from a dynamic to a solid state and abnormally accumulates at the poles, causing the segregated chromosome sets to bend around the NuMA-enriched poles. NuMA localization at the poles relies on interactions with dynein/dynactin, its coiled-coil domain, and an intrinsically disordered region (IDR). Mutagenesis experiments revealed that cation-π interactions within IDR are key for NuMA pole localization, while glutamine residues trigger the solid-state transition of NuMA upon Aurora A inhibition. We propose that maintaining the proper material properties of the spindle poles is a key step in choreographing the accurate organization of the nucleus and genome post-mitosis.
动物细胞在有丝分裂开始时解体其核膜（NE），并在有丝分裂结束时重新构建它。这个过程与纺锤体极组织密切协调：纺锤体极在有丝分裂开始时增大，在有丝分裂结束时缩小。这种协调的意义仍然未知。在这里，我们证明极光激酶A（Aurora A）在后期使一种定位于纺锤体极的蛋白质核有丝分裂器蛋白（NuMA）保持动态状态。没有极光激酶A的活性，NuMA从动态状态转变为固态，并异常地在纺锤体极积累，导致分离的染色体组围绕富含NuMA的纺锤体极弯曲。NuMA在纺锤体极的定位依赖于与动力蛋白/动力蛋白激活蛋白、其卷曲螺旋结构域和一个内在无序区域（IDR）的相互作用。诱变实验表明，IDR内的阳离子-π相互作用是NuMA纺锤体极定位的关键，而谷氨酰胺残基在极光激酶A受抑制时触发NuMA的固态转变。我们提出，维持纺锤体极的适当物质特性是精心编排有丝分裂后细胞核和基因组精确组织的关键步骤。
