Cross-regulation between Aurora B and Citron kinase controls midbody architecture in cytokinesis.

Callum Mckenzie,Janusz Debski,Pier Paolo D'Avino,Zuni I Bassi,Michal Dadlez,Marco Gottardo,Giuliano Callaini

doi:10.1098/rsob.160019

Abstract

Cytokinesis culminates in the final separation, or abscission, of the two daughter cells at the end of cell division. Abscission relies on an organelle, the midbody, which forms at the intercellular bridge and is composed of various proteins arranged in a precise stereotypic pattern. The molecular mechanisms controlling midbody organization and function, however, are obscure. Here we show that proper midbody architecture requires cross-regulation between two cell division kinases, Citron kinase (CIT-K) and Aurora B, the kinase component of the chromosomal passenger complex (CPC). CIT-K interacts directly with three CPC components and is required for proper midbody architecture and the orderly arrangement of midbody proteins, including the CPC. In addition, we show that CIT-K promotes Aurora B activity through phosphorylation of the INCENP CPC subunit at the TSS motif. In turn, Aurora B controls CIT-K localization and association with its central spindle partners through phosphorylation of CIT-K's coiled coil domain. Our results identify, for the first time, a cross-regulatory mechanism between two kinases during cytokinesis, which is crucial for establishing the stereotyped organization of midbody proteins.

Highlights

Cytokinesis controls the proper partitioning of cytoplasmic and nuclear material between the two nascent daughter cells
We show that Citron kinase (CIT-K) is required for correct chromosomal passenger complex (CPC) localization and phosphorylates the INCENP subunit of the CPC at the TSS Aurora B activation site
Electron microscopy (EM) analysis revealed that the midbody matrix was fragmented, disorganized, detached from the cortex and mis-positioned towards one of the two nascent daughter cells

Summary

Introduction

Cytokinesis controls the proper partitioning of cytoplasmic and nuclear material between the two nascent daughter cells. Defects in this process have been associated with various human diseases [1] and can cause polyploidy, which in turn can lead to chromosomal instability, a hallmark of cancer cells [2]. After anaphase onset the mitotic spindle is completely reorganized into an array of interdigitating and antiparallel microtubules, known as the central spindle [3]. Some midbody proteins are former contractile ring and central spindle components, while others are recruited after completion of furrow ingression. All these proteins show a very precise and

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Conclusion