Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.
Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9782-7. doi: 10.1073/pnas.1301328110. Epub 2013 May 28.
Cytokinesis partitions cytoplasmic and genomic materials at the end of cell division. Failure in this process causes polyploidy, which in turn can generate chromosomal instability, a hallmark of many cancers. Successful cytokinesis requires cooperative interaction between contractile ring and central spindle components, but how this cooperation is established is poorly understood. Here we show that Sticky (Sti), the Drosophila ortholog of the contractile ring component Citron kinase (CIT-K), interacts directly with two kinesins, Nebbish [the fly counterpart of human kinesin family member 14 (KIF14)] and Pavarotti [the Drosophila ortholog of human mitotic kinesin-like protein 1 (MKLP1)], and that in turn these kinesins interact with each other and with another central spindle protein, Fascetto [the fly ortholog of protein regulator of cytokinesis 1 (PRC1)]. Sti recruits Nebbish to the cleavage furrow, and both proteins are required for midbody formation and proper localization of Pavarotti and Fascetto. These functions require Sti kinase activity, indicating that Sti plays both structural and regulatory roles in midbody formation. Finally, we show that CIT-K's role in midbody formation is conserved in human cells. Our findings indicate that CIT-K is likely to act at the top of the midbody-formation hierarchy by connecting and regulating a molecular network of contractile ring components and microtubule-associated proteins.
胞质分裂将细胞质和基因组物质在细胞分裂结束时分开。这个过程的失败会导致多倍体，进而导致染色体不稳定，这是许多癌症的一个标志。成功的胞质分裂需要收缩环和中心纺锤体成分之间的协同相互作用，但这种合作是如何建立的还不清楚。在这里，我们表明果蝇Citron 激酶（CIT-K）的收缩环成分粘性（Sti）与两个驱动蛋白，Nebbish（人类驱动蛋白家族成员 14（KIF14）的果蝇对应物）和 Pavarotti（人类有丝分裂驱动蛋白样蛋白 1（MKLP1）的果蝇对应物）直接相互作用，反过来，这些驱动蛋白相互作用，并与另一个中心纺锤体蛋白 Fascetto（细胞分裂调控蛋白 1（PRC1）的果蝇对应物）相互作用。Sti 将 Nebbish 招募到分裂沟中，这两种蛋白质对于中体的形成和 Pavarotti 和 Fascetto 的正确定位都是必需的。这些功能需要 Sti 激酶活性，表明 Sti 在中体形成中发挥结构和调节作用。最后，我们表明 CIT-K 在人细胞中形成中体的作用是保守的。我们的发现表明，CIT-K 可能通过连接和调节收缩环成分和微管相关蛋白的分子网络，在中体形成的层次结构中发挥作用。
