<p>Accurate cell division relies on rapid chromosome congression. The kinetochore motor protein CENP-E/kinesin-7 is uniquely required for congression of polar chromosomes. It is currently assumed that CENP-E drives congression by gliding kinetochores along microtubules independently of their biorientation. Here, by studying chromosome movement under different levels of CENP-E activity, we favor an alternative model in which CENP-E initiates congression by promoting stabilization of end-on attachments. In this way, CENP-E accelerates congression initiation without significantly contributing to subsequent movement. Stabilization of end-on attachments on polar chromosomes without CENP-E is delayed due to Aurora kinase-mediated hyperphosphorylation of microtubule-binding proteins and expansion of the fibrous corona. CENP-E counters this by reducing Aurora B-mediated phosphorylation in a BubR1-dependent manner, thereby stabilizing initial end-on attachments, facilitating removal of the fibrous corona, and triggering biorientation-dependent chromosome movement. These findings support a unified model of chromosome movement in which congression is intrinsically coupled to biorientation.</p>

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CENP-E initiates chromosome congression by opposing Aurora kinases to promote end-on attachments

  • Kruno Vukušić,
  • Iva M. Tolić

摘要

Accurate cell division relies on rapid chromosome congression. The kinetochore motor protein CENP-E/kinesin-7 is uniquely required for congression of polar chromosomes. It is currently assumed that CENP-E drives congression by gliding kinetochores along microtubules independently of their biorientation. Here, by studying chromosome movement under different levels of CENP-E activity, we favor an alternative model in which CENP-E initiates congression by promoting stabilization of end-on attachments. In this way, CENP-E accelerates congression initiation without significantly contributing to subsequent movement. Stabilization of end-on attachments on polar chromosomes without CENP-E is delayed due to Aurora kinase-mediated hyperphosphorylation of microtubule-binding proteins and expansion of the fibrous corona. CENP-E counters this by reducing Aurora B-mediated phosphorylation in a BubR1-dependent manner, thereby stabilizing initial end-on attachments, facilitating removal of the fibrous corona, and triggering biorientation-dependent chromosome movement. These findings support a unified model of chromosome movement in which congression is intrinsically coupled to biorientation.