Mitotic Disassembly of Nuclear Pore Complexes Involves CDK1- and PLK1-Mediated Phosphorylation of Key Interconnecting Nucleoporins

• Published in: Developmental cell 2017-10, Vol.43 (2), p.141-156.e7
• Main Authors: Linder, Monika I., Köhler, Mario, Boersema, Paul, Weberruss, Marion, Wandke, Cornelia, Marino, Joseph, Ashiono, Caroline, Picotti, Paola, Antonin, Wolfram, Kutay, Ulrike
• Format: Article
• Language: English
• Subjects: CDC2 Protein Kinase; CDK1; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Nucleus - genetics; Cell Nucleus - metabolism; Cyclin-Dependent Kinases - genetics; Cyclin-Dependent Kinases - metabolism; HeLa Cells; Humans; mitosis; Mitosis - physiology; NDC1; NPC; NPC disassembly; Nuclear Envelope - genetics; Nuclear Envelope - metabolism; Nuclear Pore - genetics; Nuclear Pore - metabolism; Nuclear Pore Complex Proteins - genetics; Nuclear Pore Complex Proteins - metabolism; nucleoporin; Nup53; Nup98; Phosphorylation; PLK1; Polo-Like Kinase 1; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2017.08.020

During interphase, the nuclear envelope (NE) serves as a selective barrier between cytosol and nucleoplasm. When vertebrate cells enter mitosis, the NE is dismantled in the process of nuclear envelope breakdown (NEBD). Disassembly of nuclear pore complexes (NPCs) is a key aspect of NEBD, required for NE permeabilization and formation of a cytoplasmic mitotic spindle. Here, we show that both CDK1 and polo-like kinase 1 (PLK1) support mitotic NPC disintegration by hyperphosphorylation of Nup98, the gatekeeper nucleoporin, and Nup53, a central nucleoporin linking the inner NPC scaffold to the pore membrane. Multisite phosphorylation of Nup53 critically contributes to its liberation from its partner nucleoporins, including the pore membrane protein NDC1. Initial steps of NPC disassembly in semi-permeabilized cells can be reconstituted by a cocktail of mitotic kinases including cyclinB-CDK1, NIMA, and PLK1, suggesting that the unzipping of nucleoporin interactions by protein phosphorylation is an important principle underlying mitotic NE permeabilization. [Display omitted] •PLK1 localizes to NPCs during prophase and promotes mitotic NPC disassembly•CDK1 and PLK1 mediate hyperphosphorylation of the central linker nucleoporin Nup53•Multisite phosphorylation of Nup53 promotes the disintegration of the central NPC•Mitotic kinases induce NPC disassembly in a reconstituted system The disassembly of nuclear pore complexes (NPCs) is a key process for nuclear envelope breakdown at the onset of open mitosis in metazoan cells. Linder et al. show that multisite phosphorylation of the key interconnecting nucleoporin Nup53 by CDK1 and PLK1 is required for the timely disassembly of the central NPC framework.