Kinetochore dynein is sufficient to biorient chromosomes and remodel the outer kinetochore

Bram Prevo (), Dhanya K. Cheerambathur, William C. Earnshaw and Arshad Desai ()
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Bram Prevo: University of Edinburgh
Dhanya K. Cheerambathur: University of Edinburgh
William C. Earnshaw: University of Edinburgh
Arshad Desai: Ludwig Institute for Cancer Research

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Multiple microtubule-directed activities concentrate on mitotic chromosomes to ensure their faithful segregation. These include couplers and dynamics regulators localized at the kinetochore, the microtubule interface built on centromeric chromatin, as well as motor proteins recruited to kinetochores and chromatin. Here, we describe an in vivo approach in the C. elegans one-cell embryo in which removal of the major microtubule-directed activities on mitotic chromosomes is compared to the selective presence of individual activities. Our approach reveals that the kinetochore dynein module, comprised of cytoplasmic dynein and its kinetochore-specific adapters, is sufficient to biorient chromosomes; by contrast, this module is unable to support congression. In coordination with orientation, the dynein module directs removal of outermost kinetochore components, including dynein itself, independently of the other microtubule-directed activities and kinetochore-localized protein phosphatase 1. These observations indicate that the kinetochore dynein module is sufficient to biorient chromosomes and to direct remodeling of the outer kinetochore in a microtubule attachment state-sensitive manner.

Date: 2024
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DOI: 10.1038/s41467-024-52964-5

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