Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A.

Elena Poser,Renaud Caous,Ulrike Gruneberg,Francis A Barr

doi:10.1083/jcb.201905194

Abstract

Aurora kinases create phosphorylation gradients within the spindle during prometaphase and anaphase, thereby locally regulating factors that promote spindle organization, chromosome condensation and movement, and cytokinesis. We show that one such factor is the kinesin KIF4A, which is present along the chromosome axes throughout mitosis and the central spindle in anaphase. These two pools of KIF4A depend on condensin I and PRC1, respectively. Previous work has shown KIF4A is activated by Aurora B at the anaphase central spindle. However, whether or not chromosome-associated KIF4A bound to condensin I is regulated by Aurora kinases remain unclear. To determine the roles of the two different pools of KIF4A, we generated specific point mutants that are unable to interact with either condensin I or PRC1 or are deficient for Aurora kinase regulation. By analyzing these mutants, we show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate.

Highlights

In prometaphase and metaphase, the two Aurora kinases A and et al, 2011; Zhang et al, 2008)
Isolation of KIF4A mutants disrupted for either condensin I or protein regulator of cytokinesis 1 (PRC1) binding In anaphase, KIF4A is present midway between the segregating chromosomes in a region defined by the anaphase spindle midzone protein PRC1 (Fig. S1 A)
We find that Aurora A–dependent regulation of a pool of KIF4A recruited to the chromosome axes through interaction with condensin I is important for the congression of chromosomes into a compact metaphase plate

Summary

Introduction

The two Aurora kinases A and et al, 2011; Zhang et al, 2008). A phosphorylation site mutant form of CENP-E cannot be the kinetochores of bioriented chromosomes, enabling these to inhibited by Aurora A and traps nonbioriented chromosomes be discriminated from other attachment geometries by an error- at the spindle poles (Kapoor et al, 2006; Kim et al, 2010). This process is primarily regulated by A kinase is thought to promote chromosome concentromeric Aurora B, which is physically close enough to the gression and error correction through inhibitory mechanisms that outer kinetochore to exert its effects only in the absence of prevent trapping of chromosomes at the poles of the mitotic tension, and provides a molecular readout of biorientation spindle

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Conclusion