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

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 huma...

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Autores principales: Shrestha, Roshan L., Conti, Duccio, Tamura, Naoka, Braun, Dominique, Ramalingam, Revathy A., Cieslinski, Konstanty, Ries, Jonas, Draviam, Viji M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532248/
https://www.ncbi.nlm.nih.gov/pubmed/28751710
http://dx.doi.org/10.1038/s41467-017-00209-z
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author Shrestha, Roshan L.
Conti, Duccio
Tamura, Naoka
Braun, Dominique
Ramalingam, Revathy A.
Cieslinski, Konstanty
Ries, Jonas
Draviam, Viji M.
author_facet Shrestha, Roshan L.
Conti, Duccio
Tamura, Naoka
Braun, Dominique
Ramalingam, Revathy A.
Cieslinski, Konstanty
Ries, Jonas
Draviam, Viji M.
author_sort Shrestha, Roshan L.
collection PubMed
description 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.
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spelling pubmed-55322482017-08-01 Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells Shrestha, Roshan L. Conti, Duccio Tamura, Naoka Braun, Dominique Ramalingam, Revathy A. Cieslinski, Konstanty Ries, Jonas Draviam, Viji M. Nat Commun Article 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. Nature Publishing Group UK 2017-07-28 /pmc/articles/PMC5532248/ /pubmed/28751710 http://dx.doi.org/10.1038/s41467-017-00209-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Shrestha, Roshan L.
Conti, Duccio
Tamura, Naoka
Braun, Dominique
Ramalingam, Revathy A.
Cieslinski, Konstanty
Ries, Jonas
Draviam, Viji M.
Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells
title Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells
title_full Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells
title_fullStr Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells
title_full_unstemmed Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells
title_short Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells
title_sort aurora-b kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532248/
https://www.ncbi.nlm.nih.gov/pubmed/28751710
http://dx.doi.org/10.1038/s41467-017-00209-z
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