The Ndc80-Cdt1-Ska1 complex is a central processive kinetochore-microtubule coupling unit.

Autor:	Rahi A; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Chakraborty M; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Agarwal S, Vosberg KM; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Agarwal S, Wang AY; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., McKenney RJ; Department of Molecular and Cellular Biology, College of Biological Sciences, University of California Davis, Davis, CA, USA., Varma D; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2023 Aug 07; Vol. 222 (8). Date of Electronic Publication: 2023 Jun 02.
DOI:	10.1083/jcb.202208018
Abstrakt:	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. (© 2023 Rahi et al.)
Databáze:	MEDLINE
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