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Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP
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 stimu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323247/ https://www.ncbi.nlm.nih.gov/pubmed/37357828 http://dx.doi.org/10.1242/jcs.261096 |
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author | Ustinova, Kseniya Ruhnow, Felix Gili, Maria Surrey, Thomas |
author_facet | Ustinova, Kseniya Ruhnow, Felix Gili, Maria Surrey, Thomas |
author_sort | Ustinova, Kseniya |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10323247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-103232472023-07-07 Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP Ustinova, Kseniya Ruhnow, Felix Gili, Maria Surrey, Thomas J Cell Sci Research Article 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. The Company of Biologists Ltd 2023-06-26 /pmc/articles/PMC10323247/ /pubmed/37357828 http://dx.doi.org/10.1242/jcs.261096 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0 (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. |
spellingShingle | Research Article Ustinova, Kseniya Ruhnow, Felix Gili, Maria Surrey, Thomas Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP |
title | Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP |
title_full | Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP |
title_fullStr | Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP |
title_full_unstemmed | Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP |
title_short | Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP |
title_sort | microtubule binding of the human augmin complex is directly controlled by importins and ran-gtp |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323247/ https://www.ncbi.nlm.nih.gov/pubmed/37357828 http://dx.doi.org/10.1242/jcs.261096 |
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