Rodríguez-Herrera Noelia, Santana-Sosa Silvia, Medina-Suárez Sara, Morais-Armas Samantha, Matos-Perdomo Emiliano, Machín Félix
Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Instituto de Investigación Sanitaria de Canarias (IISC), Santa Cruz de Tenerife, Spain.
Instituto de Tecnologías Biomédicas, Universidad de La Laguna, San Cristóbal de La Laguna, Spain.
Biol Cell. 2025 May;117(5):e70011. doi: 10.1111/boc.70011.
Two major types of cell division occur in eukaryotic cells regarding the dismantlement or not of the nuclear envelope (NE) in mitosis, open and closed mitosis, respectively. In the budding yeast Saccharomyces cerevisiae, the prototypical model for closed mitosis, the Nem1-Spo7 phosphatase complex, which regulates lipid metabolism, plays a key role in coordinating NE expansion throughout the cell cycle. Indeed, Nem1 depletion leads to abnormal NE evaginations in interphase, which protrude the ribosomal DNA (rDNA) and the nucleolus. However, the specific impact of these NE and chromosome organization abnormalities during chromosome segregation in anaphase remains poorly understood.
Our study investigated chromosome segregation and NE dynamics during closed mitosis in relation to the presence or absence of Nem1. Nem1 was depleted by means of the auxin degron system. Nem1 depletion led to the formation of chromatin protrusions in interphase, particularly at the rDNA locus, as it has been reported before for nem1 mutants. These protrusions persisted into anaphase and were associated with delayed recoiling of the rDNA-bearing chromosome XII right arm, resulting in lagging chromatin during late anaphase. Additionally, cells can maintain nucleus-vacuole junctions (NVJs) during anaphase, suggesting that vacuoles may play a role in shaping NE morphology during chromosome segregation.
Our findings suggest that the Nem1-Spo7/lipin regulation of the NE size is crucial for the timely segregation of the rDNA-bearing chromosome during closed mitosis. Thus, the NE homeostasis actively contributes to chromosome segregation and the spatial organization of chromosomes in subsequent cell cycles. In addition, the persistent association between the NE and vacuoles in anaphase further underscores how cumbersome organelle interactions can become during closed mitosis, opening inspiring research avenues.
真核细胞中有两种主要的细胞分裂类型,分别是有丝分裂过程中核膜(NE)是否解体的开放式和封闭式有丝分裂。在典型的封闭式有丝分裂模型——芽殖酵母酿酒酵母中,调节脂质代谢的Nem1-Spo7磷酸酶复合物在协调整个细胞周期中核膜的扩张方面起着关键作用。事实上,缺失Nem1会导致间期核膜异常外翻,突出核糖体DNA(rDNA)和核仁。然而,在后期染色体分离过程中,这些核膜和染色体组织异常的具体影响仍知之甚少。
我们的研究调查了封闭式有丝分裂过程中与Nem1存在与否相关的染色体分离和核膜动态。通过生长素降解系统使Nem1缺失。如之前对nem1突变体的报道,缺失Nem1会导致间期染色质突出,特别是在rDNA位点。这些突出在后期持续存在,并与携带rDNA的第十二号染色体右臂延迟回缩相关,导致后期末期染色质滞后。此外,细胞在后期可以维持核-液泡连接(NVJ),这表明液泡可能在染色体分离过程中塑造核膜形态方面发挥作用。
我们的研究结果表明,Nem1-Spo7/脂素对核膜大小的调节对于封闭式有丝分裂期间携带rDNA的染色体的及时分离至关重要。因此,核膜稳态积极促进染色体分离以及后续细胞周期中染色体的空间组织。此外,后期核膜与液泡之间的持续关联进一步凸显了封闭式有丝分裂期间细胞器相互作用可能变得多么复杂,开辟了令人鼓舞的研究途径。