The minus-end depolymerase KIF2A drives flux-like treadmilling of γTuRC-uncapped microtubules

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  • dc.contributor.author Henkin, Gil
  • dc.contributor.author Brito, Cláudia
  • dc.contributor.author Thomas, Claire
  • dc.contributor.author Surrey, Thomas
  • dc.date.accessioned 2023-11-03T07:36:38Z
  • dc.date.available 2023-11-03T07:36:38Z
  • dc.date.issued 2023
  • dc.description.abstract During mitosis, microtubules in the spindle turn over continuously. At spindle poles, where microtubule minus ends are concentrated, microtubule nucleation and depolymerization, the latter required for poleward microtubule flux, happen side by side. How these seemingly antagonistic processes of nucleation and depolymerization are coordinated is not understood. Here, we reconstitute this coordination in vitro combining different pole-localized activities. We find that the spindle pole-localized kinesin-13 KIF2A is a microtubule minus-end depolymerase, in contrast to its paralog MCAK. Due to its asymmetric activity, KIF2A still allows microtubule nucleation from the γ-tubulin ring complex (γTuRC), which serves as a protective cap shielding the minus end against KIF2A binding. Efficient γTuRC uncapping requires the combined action of KIF2A and a microtubule severing enzyme, leading to treadmilling of the uncapped microtubule driven by KIF2A. Together, these results provide insight into the molecular mechanisms by which a minimal protein module coordinates microtubule nucleation and depolymerization at spindle poles consistent with their role in poleward microtubule flux.
  • dc.description.sponsorship This work was supported by the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme of the Generalitat de Catalunya, and by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001163), the UK Medical Research Council (FC001163), and the Wellcome Trust (FC001163). C. Brito was supported by EMBO long-term fellowship ALTF-883-2020 and Marie Curie fellowship TuRCReg. T. Surrey acknowledges support from the European Research Council (ERC Synergy Grant, Project 951430) and the Spanish Ministry of Science and Innovation (grant PID2019-108415GB-I00). Open Access funding provided by the Universitat Pompeu Fabra.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Henkin G, Brito C, Thomas C, Surrey T. The minus-end depolymerase KIF2A drives flux-like treadmilling of γTuRC-uncapped microtubules. J Cell Biol. 2023 Oct 2;222(10):e202304020. DOI: 10.1083/jcb.202304020
  • dc.identifier.doi http://dx.doi.org/10.1083/jcb.202304020
  • dc.identifier.issn 0021-9525
  • dc.identifier.uri http://hdl.handle.net/10230/58205
  • dc.language.iso eng
  • dc.publisher Rockefeller University Press
  • dc.relation.ispartof J Cell Biol. 2023 Oct 2;222(10):e202304020
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/951430
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-108415GB-I00
  • dc.rights © 2023 Henkin et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.title The minus-end depolymerase KIF2A drives flux-like treadmilling of γTuRC-uncapped microtubules
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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