CENP-E activation by Aurora A and B controls kinetochore fibrous corona disassembly

Susana Eibes, Girish Rajendraprasad, Claudia Guasch-Boldu, Mirela Kubat, Yulia Steblyanko and Marin Barisic ()
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Susana Eibes: Danish Cancer Institute
Girish Rajendraprasad: Danish Cancer Institute
Claudia Guasch-Boldu: Danish Cancer Institute
Mirela Kubat: Danish Cancer Institute
Yulia Steblyanko: Danish Cancer Institute
Marin Barisic: Danish Cancer Institute

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Accurate chromosome segregation in mitosis depends on multiprotein structures called kinetochores that are built on the centromeric region of sister chromatids and serve to capture mitotic spindle microtubules. In early mitosis, unattached kinetochores expand a crescent-shaped structure called fibrous corona whose function is to facilitate initial kinetochore-microtubule attachments and chromosome transport by microtubules. Subsequently, the fibrous corona must be timely disassembled to prevent segregation errors. Although recent studies provided new insights on the molecular content and mechanism of fibrous corona assembly, it remains unknown what triggers the disassembly of the outermost and dynamic layer of the kinetochore. Here, we show that Aurora A and B kinases phosphorylate CENP-E to release it from an autoinhibited state. At kinetochores, Aurora B phosphorylates CENP-E to prevent its premature removal together with other corona proteins by dynein. At the spindle poles, Aurora A phosphorylates CENP-E to promote chromosome congression and prevent accumulation of corona proteins at the centrosomes, allowing for their intracellular redistribution. Thus, we propose the Aurora A/B-CENP-E axis as a critical element of the long-sought-for mechanism of fibrous corona disassembly that is essential for accurate chromosome segregation.

Date: 2023
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DOI: 10.1038/s41467-023-41091-2

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