Cullati Sierra N, Kabeche Lilian, Kettenbach Arminja N, Gerber Scott A
Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH.
Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
J Cell Biol. 2017 Aug 7;216(8):2339-2354. doi: 10.1083/jcb.201512055. Epub 2017 Jun 19.
In mitosis, cells undergo a precisely orchestrated series of spatiotemporal changes in cytoskeletal structure to divide their genetic material. These changes are coordinated by a sophisticated network of protein-protein interactions and posttranslational modifications. In this study, we report a bifurcation in a signaling cascade of the NIMA-related kinases (Neks) Nek6, Nek7, and Nek9 that is required for the localization and function of two kinesins essential for cytokinesis, Mklp2 and Kif14. We demonstrate that a Nek9, Nek6, and Mklp2 signaling module controls the timely localization and bundling activity of Mklp2 at the anaphase central spindle. We further show that a separate Nek9, Nek7, and Kif14 signaling module is required for the recruitment of the Rho-interacting kinase citron to the anaphase midzone. Our findings uncover an anaphase-specific function for these effector kinesins that is controlled by specific Nek kinase signaling modules to properly coordinate cytokinesis.
在有丝分裂过程中，细胞经历细胞骨架结构精确编排的一系列时空变化，以分离其遗传物质。这些变化由复杂的蛋白质 - 蛋白质相互作用和翻译后修饰网络协调。在本研究中，我们报告了NIMA相关激酶（Neks）Nek6、Nek7和Nek9信号级联中的一个分支，这一分支对于胞质分裂所必需的两种驱动蛋白Mklp2和Kif14的定位和功能是必需的。我们证明，一个Nek9、Nek6和Mklp2信号模块控制Mklp2在后期中央纺锤体的及时定位和成束活性。我们进一步表明，一个单独的Nek9、Nek7和Kif14信号模块是将Rho相互作用激酶citron募集到后期中区所必需的。我们的研究结果揭示了这些效应驱动蛋白的后期特异性功能，该功能由特定的Nek激酶信号模块控制，以正确协调胞质分裂。
