NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
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- dc.contributor.author Colombo, Sabina
- dc.contributor.author Michel, Christel
- dc.contributor.author Speroni, Silvia
- dc.contributor.author Ruhnow, Felix
- dc.contributor.author Gili, Maria
- dc.contributor.author Brito, Cláudia
- dc.contributor.author Surrey, Thomas
- dc.date.accessioned 2025-05-16T05:41:15Z
- dc.date.available 2025-05-16T05:41:15Z
- dc.date.issued 2025
- dc.description.abstract Nuclear mitotic apparatus protein (NuMA) is indispensable for the mitotic functions of the major microtubule minus-end directed motor cytoplasmic dynein 1. NuMA and dynein are both essential for correct spindle pole organization. How these proteins cooperate to gather microtubule minus ends at spindle poles remains unclear. Here, we use microscopy-based in vitro reconstitutions to demonstrate that NuMA is a dynein adaptor, activating processive dynein motility together with dynein's cofactors dynactin and Lissencephaly-1 (Lis1). Additionally, we find that NuMA binds and stabilizes microtubule minus ends, allowing dynein/dynactin/NuMA to transport microtubule minus ends as cargo to other minus ends. We further show that the microtubule-nucleating γ-tubulin ring complex (γTuRC) hinders NuMA binding and that NuMA only caps minus ends of γTuRC-nucleated microtubules after γTuRC release. These results provide new mechanistic insight into how dynein, dynactin, NuMA, and Lis1 together with γTuRC and uncapping proteins cooperate to organize spindle poles in cells.
- dc.description.sponsorship T. Surrey acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 951430), from the Spanish Ministry of Science and Innovation (grants PID2019-108415GB-I00/AEI/10.13039/501100011033 and PID2022-142927NB-I00/AEI/10.13039/501100011033/FEDER, EU), and from the Departament de Recerca i Universitats de la Generalitat de Catalunya (2021-SGR2021-01224). S. Colombo was supported by FPI fellowship PRE2020-094511 from the Spanish Ministry of Science and Innovation, and C. Brito was supported by EMBO long-term fellowship ALTF-883-2020 and Marie Curie fellowship TuRCReg. Open Access funding provided by the Universitat Pompeu Fabra.
- dc.format.mimetype application/pdf
- dc.identifier.citation Colombo S, Michel C, Speroni S, Ruhnow F, Gili M, Brito C, et al. NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends. J Cell Biol. 2025 Apr 7;224(4):e202408118. DOI: 10.1083/jcb.202408118
- dc.identifier.doi http://dx.doi.org/10.1083/jcb.202408118
- dc.identifier.issn 0021-9525
- dc.identifier.uri http://hdl.handle.net/10230/70415
- dc.language.iso eng
- dc.publisher Rockefeller University Press
- dc.relation.ispartof J Cell Biol. 2025 Apr 7;224(4):e202408118
- 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 © 2025 Colombo et al. This work is licensed under a Creative Commons Attribution 4.0 International License (http://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.subject.keyword Biochemistry
- dc.subject.keyword Biophysics
- dc.subject.keyword Cell cycle and division
- dc.subject.keyword Cytoskeleton
- dc.title NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion