Regulation of minimal spindle midzone organization by mitotic kinases
Abstract During cell division, the microtubule cytoskeleton undergoes dramatic cell cycle-driven reorganizations of its architecture. Coordinated by changes in the phosphorylation patterns of a multitude of microtubule associated proteins, the mitotic spindle first self-assembles to capture the chro...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53500-1 |
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| author | Wei Ming Lim Wei-Xiang Chew Arianna Esposito Verza Marion Pesenti Andrea Musacchio Thomas Surrey |
| author_facet | Wei Ming Lim Wei-Xiang Chew Arianna Esposito Verza Marion Pesenti Andrea Musacchio Thomas Surrey |
| author_sort | Wei Ming Lim |
| collection | DOAJ |
| description | Abstract During cell division, the microtubule cytoskeleton undergoes dramatic cell cycle-driven reorganizations of its architecture. Coordinated by changes in the phosphorylation patterns of a multitude of microtubule associated proteins, the mitotic spindle first self-assembles to capture the chromosomes and then reorganizes in anaphase as the chromosomes are segregated. A key protein for this reorganization is PRC1 which is differentially phosphorylated by the mitotic kinases CDK1 and PLK1. How the phosphorylation state of PRC1 orchestrates spindle reorganization is not understood mechanistically. Here, we reconstitute in vitro the transition between metaphase and anaphase-like microtubule architectures triggered by the changes in PRC1 phosphorylation. We find that whereas PLK1 regulates its own recruitment by PRC1, CDK1 controls the affinity of PRC1 for antiparallel microtubule binding. Dephosphorylation of CDK1-phosphorylated PRC1 is required and sufficient to trigger the reorganization of a minimal anaphase midzone in the presence of the midzone length controlling kinesin KIF4A. These results demonstrate how phosphorylation-controlled affinity changes regulate the architecture of active microtubule networks, providing new insight into the mechanistic underpinnings of the cell cycle-driven reorganization of the central spindle during mitosis. |
| format | Article |
| id | doaj-art-d454476d561b476ebdc59947e9765265 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d454476d561b476ebdc59947e97652652025-08-20T02:18:33ZengNature PortfolioNature Communications2041-17232024-10-0115111710.1038/s41467-024-53500-1Regulation of minimal spindle midzone organization by mitotic kinasesWei Ming Lim0Wei-Xiang Chew1Arianna Esposito Verza2Marion Pesenti3Andrea Musacchio4Thomas Surrey5Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Carrer del Dr. Aiguader 88Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Carrer del Dr. Aiguader 88Department of Mechanistic Cell Biology, Max Planck Institute of Molecular PhysiologyDepartment of Mechanistic Cell Biology, Max Planck Institute of Molecular PhysiologyDepartment of Mechanistic Cell Biology, Max Planck Institute of Molecular PhysiologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Carrer del Dr. Aiguader 88Abstract During cell division, the microtubule cytoskeleton undergoes dramatic cell cycle-driven reorganizations of its architecture. Coordinated by changes in the phosphorylation patterns of a multitude of microtubule associated proteins, the mitotic spindle first self-assembles to capture the chromosomes and then reorganizes in anaphase as the chromosomes are segregated. A key protein for this reorganization is PRC1 which is differentially phosphorylated by the mitotic kinases CDK1 and PLK1. How the phosphorylation state of PRC1 orchestrates spindle reorganization is not understood mechanistically. Here, we reconstitute in vitro the transition between metaphase and anaphase-like microtubule architectures triggered by the changes in PRC1 phosphorylation. We find that whereas PLK1 regulates its own recruitment by PRC1, CDK1 controls the affinity of PRC1 for antiparallel microtubule binding. Dephosphorylation of CDK1-phosphorylated PRC1 is required and sufficient to trigger the reorganization of a minimal anaphase midzone in the presence of the midzone length controlling kinesin KIF4A. These results demonstrate how phosphorylation-controlled affinity changes regulate the architecture of active microtubule networks, providing new insight into the mechanistic underpinnings of the cell cycle-driven reorganization of the central spindle during mitosis.https://doi.org/10.1038/s41467-024-53500-1 |
| spellingShingle | Wei Ming Lim Wei-Xiang Chew Arianna Esposito Verza Marion Pesenti Andrea Musacchio Thomas Surrey Regulation of minimal spindle midzone organization by mitotic kinases Nature Communications |
| title | Regulation of minimal spindle midzone organization by mitotic kinases |
| title_full | Regulation of minimal spindle midzone organization by mitotic kinases |
| title_fullStr | Regulation of minimal spindle midzone organization by mitotic kinases |
| title_full_unstemmed | Regulation of minimal spindle midzone organization by mitotic kinases |
| title_short | Regulation of minimal spindle midzone organization by mitotic kinases |
| title_sort | regulation of minimal spindle midzone organization by mitotic kinases |
| url | https://doi.org/10.1038/s41467-024-53500-1 |
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