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...
| Autores: | ; ; ; ; ; ; |
|---|---|
| Tipo de documento: | Artículo |
| Estado: | Published version |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/70415 |
| Acceso en línea: | http://hdl.handle.net/10230/70415 http://dx.doi.org/10.1083/jcb.202408118 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Biochemistry Biophysics Cell cycle and division Cytoskeleton |
| _version_ | 1878740635923513344 |
|---|---|
| author | Colombo, Sabina |
| author2 | Michel, Christel Speroni, Silvia Ruhnow, Felix Gili, Maria Brito, Cláudia Surrey, Thomas |
| author2_role | author author author author author author |
| author_browse | Brito, Cláudia Colombo, Sabina Gili, Maria Michel, Christel Ruhnow, Felix Speroni, Silvia Surrey, Thomas |
| author_facet | Colombo, Sabina Michel, Christel Speroni, Silvia Ruhnow, Felix Gili, Maria Brito, Cláudia Surrey, Thomas |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_d6a4cd0531021b8397e924aa3dfa3ea6 |
| institution | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:10230/70415 |
| publishDate | 2025 |
| publishDateSort | 2025 |
| publisher | Rockefeller University Press |
| publisherStr | Rockefeller University Press |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends Colombo, Sabina Michel, Christel Speroni, Silvia Ruhnow, Felix Gili, Maria Brito, Cláudia Surrey, Thomas Biochemistry Biophysics Cell cycle and division Cytoskeleton 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. 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 Press http://hdl.handle.net/10230/70415 http://dx.doi.org/10.1083/jcb.202408118 |
| 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 |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Biochemistry Biophysics Cell cycle and division Cytoskeleton |
| topic_facet | Biochemistry Biophysics Cell cycle and division Cytoskeleton |
| url | http://hdl.handle.net/10230/70415 http://dx.doi.org/10.1083/jcb.202408118 |