Nkoula Sylvia Nkombo, Velez-Aguilera Griselda, Ossareh-Nazari Batool, Hove Lucie Van, Ayuso Cristina, Legros Véronique, Chevreux Guillaume, Thomas Laura, Seydoux Géraldine, Askjaer Peter, Pintard Lionel
bioRxiv. 2023 Feb 22:2023.02.21.528438. doi: 10.1101/2023.02.21.528438.
The nuclear envelope, which protects and organizes the interphase genome, is dismantled during mitosis. In the zygote, nuclear envelope breakdown (NEBD) of the parental pronuclei is spatially and temporally regulated during mitosis to promote the unification of the parental genomes. During NEBD, Nuclear Pore Complex (NPC) disassembly is critical for rupturing the nuclear permeability barrier and removing the NPCs from the membranes near the centrosomes and between the juxtaposed pronuclei. By combining live imaging, biochemistry, and phosphoproteomics, we characterized NPC disassembly and unveiled the exact role of the mitotic kinase PLK-1 in this process. We show that PLK-1 disassembles the NPC by targeting multiple NPC sub-complexes, including the cytoplasmic filaments, the central channel, and the inner ring. Notably, PLK-1 is recruited to and phosphorylates intrinsically disordered regions of several multivalent linker nucleoporins, a mechanism that appears to be an evolutionarily conserved driver of NPC disassembly during mitosis. (149/150 words).
ONE-SENTENCE SUMMARY: PLK-1 targets intrinsically disordered regions of multiple multivalent nucleoporins to dismantle the nuclear pore complexes in the zygote.
保护和组织间期基因组的核膜在有丝分裂期间会解体。在受精卵中，亲代原核的核膜破裂（NEBD）在有丝分裂期间受到时空调节，以促进亲代基因组的统一。在NEBD期间，核孔复合体（NPC）的解体对于打破核通透性屏障以及从中心体附近和并列原核之间的膜上移除NPC至关重要。通过结合实时成像、生物化学和磷酸化蛋白质组学，我们对NPC解体进行了表征，并揭示了有丝分裂激酶PLK-1在此过程中的具体作用。我们表明，PLK-1通过靶向多个NPC亚复合体来拆解NPC，包括细胞质细丝、中央通道和内环。值得注意的是，PLK-1被招募到几个多价连接核孔蛋白的内在无序区域并使其磷酸化，这一机制似乎是有丝分裂期间NPC解体的一个进化保守驱动因素。（149/150字）
PLK-1靶向多个多价核孔蛋白的内在无序区域以拆解受精卵中的核孔复合体。
