Walters Alison D, May Christopher K, Dauster Emma S, Cinquin Bertrand P, Smith Elizabeth A, Robellet Xavier, D'Amours Damien, Larabell Carolyn A, Cohen-Fix Orna
Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Curr Biol. 2014 Dec 1;24(23):2861-7. doi: 10.1016/j.cub.2014.10.029. Epub 2014 Nov 20.
Abnormal nuclear size and shape are hallmarks of aging and cancer. However, the mechanisms regulating nuclear morphology and nuclear envelope (NE) expansion are poorly understood. In metazoans, the NE disassembles prior to chromosome segregation and reassembles at the end of mitosis. In budding yeast, the NE remains intact. The nucleus elongates as chromosomes segregate and then divides at the end of mitosis to form two daughter nuclei without NE disassembly. The budding yeast nucleus also undergoes remodeling during a mitotic arrest; the NE continues to expand despite the pause in chromosome segregation, forming a nuclear extension, or "flare," that encompasses the nucleolus. The distinct nucleolar localization of the mitotic flare indicates that the NE is compartmentalized and that there is a mechanism by which NE expansion is confined to the region adjacent to the nucleolus. Here we show that mitotic flare formation is dependent on the yeast polo kinase Cdc5. This function of Cdc5 is independent of its known mitotic roles, including rDNA condensation. High-resolution imaging revealed that following Cdc5 inactivation, nuclei expand isometrically rather than forming a flare, indicating that Cdc5 is needed for NE compartmentalization. Even in an uninterrupted cell cycle, a small NE expansion occurs adjacent to the nucleolus prior to anaphase in a Cdc5-dependent manner. Our data provide the first evidence that polo kinase, a key regulator of mitosis, plays a role in regulating nuclear morphology and NE expansion.
细胞核大小和形状异常是衰老和癌症的标志。然而，调节核形态和核膜（NE）扩张的机制仍知之甚少。在后生动物中，核膜在染色体分离之前解体，并在有丝分裂结束时重新组装。在芽殖酵母中，核膜保持完整。随着染色体分离，细胞核伸长，然后在有丝分裂结束时分裂形成两个子细胞核，而核膜不解体。芽殖酵母的细胞核在有丝分裂停滞期间也会发生重塑；尽管染色体分离暂停，核膜仍继续扩张，形成一个包含核仁的核延伸部分或“耀斑”。有丝分裂耀斑独特的核仁定位表明核膜是分隔的，并且存在一种机制将核膜扩张限制在核仁附近的区域。在这里，我们表明有丝分裂耀斑的形成依赖于酵母 polo 激酶 Cdc5。Cdc5 的这一功能独立于其已知的有丝分裂作用，包括核糖体 DNA（rDNA）凝聚。高分辨率成像显示，Cdc5 失活后，细胞核等比例扩张而不是形成耀斑，这表明 Cdc5 是核膜分隔所必需的。即使在不间断的细胞周期中，在后期之前，核仁附近也会以 Cdc5 依赖的方式发生小的核膜扩张。我们的数据首次证明，有丝分裂的关键调节因子 polo 激酶在调节核形态和核膜扩张中发挥作用。
