Regulation of minimal spindle midzone organization by mitotic kinases

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  • dc.contributor.author Lim, Wei Ming
  • dc.contributor.author Chew, Wei-Xiang
  • dc.contributor.author Esposito Verza, Arianna
  • dc.contributor.author Pesenti, Marion
  • dc.contributor.author Musacchio, Andrea
  • dc.contributor.author Surrey, Thomas
  • dc.date.accessioned 2025-01-31T07:55:13Z
  • dc.date.available 2025-01-31T07:55:13Z
  • dc.date.issued 2024
  • dc.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.
  • dc.description.sponsorship We acknowledge support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI /10.13039/501100011033), and the Generalitat de Catalunya through the CERCA program. We are grateful to the CRG Core Technologies Program for their support and assistance.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 951430; T.S. and A.M.) and received support from the Spanish Ministry of Science and Innovation (grants PID2019-108415GB-I00 / AEI / 10.13039/501100011033 and PID2022-142927NB-I00 / AEI / 10.13039/501100011033; T.S.). W.-X.C. was supported by a Human Frontier Science Program fellowship (HFSP LT000682/2020-C).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Lim WM, Chew WX, Esposito Verza A, Pesenti M, Musacchio A, Surrey T. Regulation of minimal spindle midzone organization by mitotic kinases. Nat Commun. 2024 Oct 29;15(1):9213. DOI: 10.1038/s41467-024-53500-1
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-024-53500-1
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/69405
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Commun. 2024 Oct 29;15(1):9213
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/951430
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-108415GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-142927NB-I00
  • dc.rights © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.title Regulation of minimal spindle midzone organization by mitotic kinases
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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