Kapoor Sukriti, Adhikary Kuheli, Kotak Sachin
Department of Microbiology and Cell Biology (MCB), Indian Institute of Science (IISc), Bangalore 560012, India.
Department of Microbiology and Cell Biology (MCB), Indian Institute of Science (IISc), Bangalore 560012, India.
Cell Rep. 2023 Dec 26;42(12):113495. doi: 10.1016/j.celrep.2023.113495. Epub 2023 Nov 22.
Nuclear envelope (NE) disassembly during mitosis is critical to ensure faithful segregation of the genetic material. NE disassembly is a phosphorylation-dependent process wherein mitotic kinases hyper-phosphorylate lamina and nucleoporins to initiate nuclear envelope breakdown (NEBD). In this study, we uncover an unexpected role of the PP2A phosphatase B55 in NEBD during the first embryonic division of Caenorhabditis elegans embryo. B55 depletion delays NE permeabilization and stabilizes lamina and nucleoporins. As a result, the merging of parental genomes and chromosome segregation is impaired. NEBD defect upon B55 depletion is not due to delayed mitotic onset or mislocalization of mitotic kinases. Importantly, we demonstrate that microtubule-dependent mechanical forces synergize with B55 for efficient NEBD. Finally, our data suggest that the lamin LMN-1 is likely a bona fide target of PP2A-B55. These findings establish a model highlighting biochemical crosstalk between kinases, PP2A-B55 phosphatase, and microtubule-generated mechanical forces in timely NE dissolution.
有丝分裂期间核膜（NE）的解体对于确保遗传物质的准确分离至关重要。核膜解体是一个磷酸化依赖的过程，其中有丝分裂激酶使核纤层蛋白和核孔蛋白过度磷酸化，从而引发核膜破裂（NEBD）。在本研究中，我们发现了蛋白磷酸酶2A（PP2A）的B55亚基在秀丽隐杆线虫胚胎第一次胚胎分裂期间的核膜破裂过程中发挥了意想不到的作用。B55亚基的缺失会延迟核膜通透性的改变，并使核纤层蛋白和核孔蛋白稳定。结果，亲代基因组的融合和染色体分离受到损害。B55亚基缺失时的核膜破裂缺陷并非由于有丝分裂起始延迟或有丝分裂激酶的定位错误。重要的是，我们证明微管依赖的机械力与B55协同作用以实现有效的核膜破裂。最后，我们的数据表明核纤层蛋白LMN-1可能是PP2A-B55的真正靶点。这些发现建立了一个模型，突出了激酶、PP2A-B55磷酸酶和微管产生的机械力之间在核膜及时解体过程中的生化相互作用。
