Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP

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• dc.contributor.author Ustinova, Kseniya
• dc.contributor.author Ruhnow, Felix
• dc.contributor.author Gili, Maria
• dc.contributor.author Surrey, Thomas
• dc.date.accessioned 2023-10-17T06:19:26Z
• dc.date.available 2023-10-17T06:19:26Z
• dc.date.issued 2023
• dc.description.abstract Mitotic spindle assembly during cell division is a highly regulated process. Ran-GTP produced around chromosomes controls the activity of a multitude of spindle assembly factors by releasing them from inhibitory interaction with importins. A major consequence of Ran-GTP regulation is the local stimulation of branched microtubule nucleation around chromosomes, which is mediated by the augmin complex (composed of the eight subunits HAUS1-HAUS8), a process that is crucially important for correct spindle assembly. However, augmin is not known to be a direct target of the Ran-GTP pathway, raising the question of how its activity is controlled. Here, we present the in vitro reconstitution of Ran-GTP-regulated microtubule binding of the human augmin complex. We demonstrate that importins directly bind to augmin, which prevents augmin from binding to microtubules. Ran-GTP relieves this inhibition. Therefore, the augmin complex is a direct target of the Ran-GTP pathway, suggesting that branching microtubule nucleation is directly regulated by the Ran-GTP gradient around chromosomes in dividing cells.
• 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 programme. We are grateful to the CRG Core Technologies Programme for their support and assistance in this work. T.S also 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 European Research Council. Deposited in PMC for immediate release.
• dc.format.mimetype application/pdf
• dc.identifier.citation Ustinova K, Ruhnow F, Gili M, Surrey T. Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP. J Cell Sci. 2023 Jun 15;136(12):jcs261096. DOI: 10.1242/jcs.261096
• dc.identifier.doi http://dx.doi.org/10.1242/jcs.261096
• dc.identifier.issn 0021-9533
• dc.identifier.uri http://hdl.handle.net/10230/58078
• dc.language.iso eng
• dc.publisher Company of Biologists
• dc.relation.ispartof J Cell Sci. 2023 Jun 15;136(12):jcs261096
• 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. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0
• dc.subject.keyword In vitro reconstitution
• dc.subject.keyword HAUS complex
• dc.subject.keyword Importins
• dc.subject.keyword Microtubule nucleation
• dc.subject.keyword NLS
• dc.subject.keyword Ran
• dc.title Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion