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

Nat Commun. 2017 Jul 28;8(1):150. doi: 10.1038/s41467-017-00209-z.

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.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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase B / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Kinetochores / metabolism*
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism*
  • Phosphoric Monoester Hydrolases / metabolism
  • Protein Binding
  • RNA Interference
  • Signal Transduction*
  • Time-Lapse Imaging / methods

Substances

  • Cell Cycle Proteins
  • KNSTRN protein, human
  • Microtubule-Associated Proteins
  • SPAG5 protein, human
  • Aurora Kinase B
  • Phosphoric Monoester Hydrolases