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

Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells.
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DOI:
10.1038/s41467-017-00209-z
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发表时间:
2017-07-28
影响因子:
16.6
通讯作者:
Draviam VM
Draviam VM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Shrestha RL;Conti D;Tamura N;Braun D;Ramalingam RA;Cieslinski K;Ries J;Draviam VM

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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.
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