McKenzie Callum, Bassi Zuni I, Debski Janusz, Gottardo Marco, Callaini Giuliano, Dadlez Michal, D'Avino Pier Paolo
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Warszawa 02-106, Poland.
Open Biol. 2016 Mar;6(3). doi: 10.1098/rsob.160019.
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.
胞质分裂在细胞分裂末期两个子细胞的最终分离（即缢裂）时达到顶峰。缢裂依赖于一种细胞器——中间体，它在细胞间桥处形成，由以精确的刻板模式排列的各种蛋白质组成。然而，控制中间体组织和功能的分子机制尚不清楚。在这里，我们表明，适当的中间体结构需要两种细胞分裂激酶——西特龙激酶（CIT-K）和染色体乘客复合体（CPC）的激酶成分极光激酶B之间的交叉调节。CIT-K直接与三种CPC成分相互作用，是适当的中间体结构和包括CPC在内的中间体蛋白质有序排列所必需的。此外，我们表明，CIT-K通过在TSS基序处磷酸化INCENP CPC亚基来促进极光激酶B的活性。反过来，极光激酶B通过磷酸化CIT-K的卷曲螺旋结构域来控制CIT-K的定位及其与中央纺锤体伙伴的结合。我们的结果首次确定了胞质分裂过程中两种激酶之间的交叉调节机制，这对于建立中间体蛋白质的刻板组织至关重要。
