NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends

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 spind...

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Autores: Colombo, Sabina, Michel, Christel, Speroni, Silvia, Ruhnow, Felix, Gili, Maria, Brito, Cláudia, Surrey, Thomas
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/70415
Acceso en línea:http://hdl.handle.net/10230/70415
http://dx.doi.org/10.1083/jcb.202408118
Access Level:acceso abierto
Palabra clave:Biochemistry
Biophysics
Cell cycle and division
Cytoskeleton
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spelling NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus endsColombo, SabinaMichel, ChristelSperoni, SilviaRuhnow, FelixGili, MariaBrito, CláudiaSurrey, ThomasBiochemistryBiophysicsCell cycle and divisionCytoskeletonNuclear 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.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.Rockefeller University Press202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/70415http://dx.doi.org/10.1083/jcb.202408118reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésJ Cell Biol. 2025 Apr 7;224(4):e202408118info:eu-repo/grantAgreement/EC/H2020/951430info:eu-repo/grantAgreement/ES/2PE/PID2019-108415GB-I00info:eu-repo/grantAgreement/ES/3PE/PID2022-142927NB-I00© 2025 Colombo et al. This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0).http://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/704152026-06-12T07:21:37Z
dc.title.none.fl_str_mv NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
title NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
spellingShingle NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
Colombo, Sabina
Biochemistry
Biophysics
Cell cycle and division
Cytoskeleton
title_short NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
title_full NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
title_fullStr NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
title_full_unstemmed NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
title_sort NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
dc.creator.none.fl_str_mv Colombo, Sabina
Michel, Christel
Speroni, Silvia
Ruhnow, Felix
Gili, Maria
Brito, Cláudia
Surrey, Thomas
author Colombo, Sabina
author_facet Colombo, Sabina
Michel, Christel
Speroni, Silvia
Ruhnow, Felix
Gili, Maria
Brito, Cláudia
Surrey, Thomas
author_role author
author2 Michel, Christel
Speroni, Silvia
Ruhnow, Felix
Gili, Maria
Brito, Cláudia
Surrey, Thomas
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Biochemistry
Biophysics
Cell cycle and division
Cytoskeleton
topic Biochemistry
Biophysics
Cell cycle and division
Cytoskeleton
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/70415
http://dx.doi.org/10.1083/jcb.202408118
url http://hdl.handle.net/10230/70415
http://dx.doi.org/10.1083/jcb.202408118
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv J Cell Biol. 2025 Apr 7;224(4):e202408118
info:eu-repo/grantAgreement/EC/H2020/951430
info:eu-repo/grantAgreement/ES/2PE/PID2019-108415GB-I00
info:eu-repo/grantAgreement/ES/3PE/PID2022-142927NB-I00
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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