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

• Published in: Nature communications Vol. 8; no. 1; pp. 150 - 13
• Main Authors: Shrestha, Roshan L., Conti, Duccio, Tamura, Naoka, Braun, Dominique, Ramalingam, Revathy A., Cieslinski, Konstanty, Ries, Jonas, Draviam, Viji M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.07.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/80/641/1655; 631/80/641/2002; Aurora Kinase B - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromatin; Chromosomes; Conversion; HeLa Cells; Humanities and Social Sciences; Humans; Immunoblotting; Kinetochores - metabolism; Microscopy, Fluorescence; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; multidisciplinary; Phosphoric Monoester Hydrolases - metabolism; Protein Binding; RNA Interference; Science; Science (multidisciplinary); Signal Transduction; Time-Lapse Imaging - methods
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-00209-z

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. Human chromosomes are captured along microtubule walls and then tethered to microtubule-ends through a multi-step end-on conversion process. Here the authors show that Aurora-B regulates end-on conversion in human cells and establish a late role for Astrin-SKAP complex in the end-on conversion process.