The Ndc80-Cdt1-Ska1 complex is a central processive kinetochore-microtubule coupling unit
© 2023 Rahi et al..
It is known that microtubule-binding proteins including the Ska1 complex and the DNA replication licensing factor, Cdt1, enable the kinetochore-localized Ndc80 complex to form robust kinetochore-microtubule attachments. However, it is not clear how the Ndc80 complex is stably coupled to dynamic spindle microtubule plus-ends. Here, we have developed a conditional auxin-inducible degron approach to reveal a function for Cdt1 in chromosome segregation and kinetochore-microtubule interactions that is separable from its role in DNA replication licensing. Further, we demonstrate that a direct interaction between Cdt1 and Ska1 is required for recruiting Cdt1 to kinetochores and spindle microtubules. Cdt1 phosphorylation by Cdk1 kinase is critical for Ska1 binding, kinetochore-microtubule attachments, and mitotic progression. Furthermore, we show that Cdt1 synergizes with Ndc80 and Ska1 for microtubule binding, including forming a diffusive, tripartite Ndc80-Cdt1-Ska1 complex that can processively track dynamic microtubule plus-ends in vitro. Taken together, our data identify the Ndc80-Cdt1-Ska1 complex as a central molecular unit that can promote processive bidirectional tip-tracking of microtubules by kinetochores.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:222 |
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| Enthalten in: |
The Journal of cell biology - 222(2023), 8 vom: 07. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rahi, Amit [VerfasserIn] |
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| Links: |
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| Themen: |
Cell Cycle Proteins |
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| Anmerkungen: |
Date Completed 05.06.2023 Date Revised 03.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1083/jcb.202208018 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357674871 |
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| 245 | 1 | 4 | |a The Ndc80-Cdt1-Ska1 complex is a central processive kinetochore-microtubule coupling unit |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 Rahi et al. | ||
| 520 | |a It is known that microtubule-binding proteins including the Ska1 complex and the DNA replication licensing factor, Cdt1, enable the kinetochore-localized Ndc80 complex to form robust kinetochore-microtubule attachments. However, it is not clear how the Ndc80 complex is stably coupled to dynamic spindle microtubule plus-ends. Here, we have developed a conditional auxin-inducible degron approach to reveal a function for Cdt1 in chromosome segregation and kinetochore-microtubule interactions that is separable from its role in DNA replication licensing. Further, we demonstrate that a direct interaction between Cdt1 and Ska1 is required for recruiting Cdt1 to kinetochores and spindle microtubules. Cdt1 phosphorylation by Cdk1 kinase is critical for Ska1 binding, kinetochore-microtubule attachments, and mitotic progression. Furthermore, we show that Cdt1 synergizes with Ndc80 and Ska1 for microtubule binding, including forming a diffusive, tripartite Ndc80-Cdt1-Ska1 complex that can processively track dynamic microtubule plus-ends in vitro. Taken together, our data identify the Ndc80-Cdt1-Ska1 complex as a central molecular unit that can promote processive bidirectional tip-tracking of microtubules by kinetochores | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 650 | 7 | |a Microtubule-Associated Proteins |2 NLM | |
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| 650 | 7 | |a Chromosomal Proteins, Non-Histone |2 NLM | |
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| 700 | 1 | |a Agarwal, Shivangi |e verfasserin |4 aut | |
| 700 | 1 | |a Vosberg, Kristen M |e verfasserin |4 aut | |
| 700 | 1 | |a Agarwal, Shivani |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Annie Y |e verfasserin |4 aut | |
| 700 | 1 | |a McKenney, Richard J |e verfasserin |4 aut | |
| 700 | 1 | |a Varma, Dileep |e verfasserin |4 aut | |
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