Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells

Roshan L. Shrestha, Duccio Conti, Naoka Tamura, Dominique Braun, Revathy A. Ramalingam, Konstanty Cieslinski, Jonas Ries and Viji M. Draviam ()
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Roshan L. Shrestha: University of Cambridge
Duccio Conti: University of Cambridge
Naoka Tamura: University of Cambridge
Dominique Braun: University of Cambridge
Revathy A. Ramalingam: Queen Mary University of London
Konstanty Cieslinski: Cell Biology and Biophysics Unit
Jonas Ries: Cell Biology and Biophysics Unit
Viji M. Draviam: University of Cambridge

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Human chromosomes are captured along microtubule walls (lateral attachment) and then tethered to microtubule-ends (end-on attachment) through a multi-step end-on conversion process. Upstream regulators that orchestrate this remarkable change in the plane of kinetochore-microtubule attachment in human cells are not known. By tracking kinetochore movements and using kinetochore markers specific to attachment status, we reveal a spatially defined role for Aurora-B kinase in retarding the end-on conversion process. To understand how Aurora-B activity is counteracted, we compare the roles of two outer-kinetochore bound phosphatases and find that BubR1-associated PP2A, unlike KNL1-associated PP1, plays a significant role in end-on conversion. Finally, we uncover a novel role for Aurora-B regulated Astrin-SKAP complex in ensuring the correct plane of kinetochore-microtubule attachment. Thus, we identify Aurora-B as a key upstream regulator of end-on conversion in human cells and establish a late role for Astrin-SKAP complex in the end-on conversion process.

Date: 2017
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DOI: 10.1038/s41467-017-00209-z

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