Mechanisms of Nuclear Pore Complex disassembly by the mitotic Polo-Like Kinase 1 (PLK-1) in C. elegans embryos

Nkombo Nkoula, S.; Velez-Aguilera, G.; Ossareh-Nazari, B.; Van Hove, L.; Ayuso, C.; Legros, V.; Chevreux, G.; Thomas, L.; Seydoux, G.; Askjaer, P.; PINTARD, L.

doi:10.1101/2023.02.21.528438

bioRxiv · 10.1101/2023.02.21.528438

Mechanisms of Nuclear Pore Complex disassembly by the mitotic Polo-Like Kinase 1 (PLK-1) in C. elegans embryos

Nkombo Nkoula, S.·Velez-Aguilera, G.·Ossareh-Nazari, B.·Van Hove, L.·Ayuso, C.·Legros, V.·Chevreux, G.·Thomas, L.·Seydoux, G.·Askjaer, P.·PINTARD, L.

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Abstract

The nuclear envelope, which protects and organizes the interphase genome, is dismantled during mitosis. In the C. elegans 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 SummaryPLK-1 targets intrinsically disordered regions of multiple multivalent nucleoporins to dismantle the nuclear pore complexes in the C. elegans zygote.

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Nkombo Nkoula, S., Velez-Aguilera, G., Ossareh-Nazari, B., Van Hove, L., Ayuso, C., Legros, V., Chevreux, G., Thomas, L., Seydoux, G., Askjaer, P., PINTARD, L.. 2023-02-22. Mechanisms of Nuclear Pore Complex disassembly by the mitotic Polo-Like Kinase 1 (PLK-1) in C. elegans embryos. https://doi.org/10.1101/2023.02.21.528438

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