Cross-regulation between Aurora B and Citron kinase controls midbody architecture in cytokinesis.
Cross-regulation between Aurora B and Citron kinase controls midbody architecture in cytokinesis.
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DOI：
10.1098/rsob.160019
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发表时间：
2016-03
期刊：
影响因子：
5.8
通讯作者：
D'Avino PP
中科院分区：
文献类型：
--
作者：
McKenzie C;Bassi ZI;Debski J;Gottardo M;Callaini G;Dadlez M;D'Avino PP
胞质分裂在细胞分裂结束时两个子细胞的最终分离或分裂中达到高潮。脱落依赖于一个细胞器，即中间体，它形成于细胞间桥，由各种蛋白质组成，以精确的定型模式排列。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个细胞分裂激酶，柠檬激酶（CIT-K）和极光B，染色体乘客复合物（CPC）的激酶成分之间的交叉调节。CIT-K直接与三种CPC组分相互作用，并且是适当的中间体结构和中间体蛋白（包括CPC）有序排列所必需的。此外，我们表明，CIT-K促进极光B活性通过磷酸化的INCENP CPC亚基在TSS基序。反过来，Aurora B通过CIT-K卷曲螺旋结构域的磷酸化控制CIT-K定位和与其中央纺锤体配偶体的结合。我们的研究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的定型组织至关重要。
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.