Astrin-SKAP Complex Reconstitution Reveals Its Kinetochore Interaction with Microtubule-bound Ndc80

Overview

Journal Elife

Specialty Biology

Date 2017 Aug 26

PMID 28841134

Citations 28

Authors

David M Kern

Julie K Monda

Kuan-Chung Su

Elizabeth M Wilson-Kubalek

Iain M Cheeseman

Affiliations

Soon will be listed here.

Abstract

Chromosome segregation requires robust interactions between the macromolecular kinetochore structure and dynamic microtubule polymers. A key outstanding question is how kinetochore-microtubule attachments are modulated to ensure that bi-oriented attachments are selectively stabilized and maintained. The Astrin-SKAP complex localizes preferentially to properly bi-oriented sister kinetochores, representing the final outer kinetochore component recruited prior to anaphase onset. Here, we reconstitute the 4-subunit Astrin-SKAP complex, including a novel MYCBP subunit. Our work demonstrates that the Astrin-SKAP complex contains separable kinetochore localization and microtubule binding domains. In addition, through cross-linking analysis in human cells and biochemical reconstitution, we show that the Astrin-SKAP complex binds synergistically to microtubules with the Ndc80 complex to form an integrated interface. We propose a model in which the Astrin-SKAP complex acts together with the Ndc80 complex to stabilize correctly formed kinetochore-microtubule interactions.

Citing Articles

CENcyclopedia: Dynamic Landscape of Kinetochore Architecture Throughout the Cell Cycle.

Chen Y, Kilic E, Wang E, Rossman W, Suzuki A bioRxiv. 2024; .

PMID: 39677682 PMC: 11643120. DOI: 10.1101/2024.12.05.627000.

SKAP binding to microtubules reduces friction at the kinetochore-microtubule interface and increases attachment stability under force.

Rosas-Salvans M, Rux C, Das M, Dumont S bioRxiv. 2024; .

PMID: 39149232 PMC: 11326240. DOI: 10.1101/2024.08.08.607154.

Liquid-liquid phase separation of microtubule-binding proteins in the regulation of spindle assembly.

Sun S, Yang Y, Zhou J, Liu P Cell Prolif. 2024; 57(10):e13649.

PMID: 38736355 PMC: 11471393. DOI: 10.1111/cpr.13649.

Search for chromosomal instability aiding variants reveal naturally occurring kinetochore gene variants that perturb chromosome segregation.

Islam A, Manjarrez-Gonzalez J, Song X, Gore T, Draviam V iScience. 2024; 27(3):109007.

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NamiRNA-mediated high expression of KNSTRN correlates with poor prognosis and immune infiltration in hepatocellular carcinoma.

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