A bifurcated signaling cascade of NIMA-related kinases controls distinct kinesins in anaphase

Abstract

A signaling module of NIMA-related kinases (Neks) regulates two kinesins, Mklp2 and Kif14, to spatiotemporally coordinate their subcellular localizations and activities. This is important for faithful completion of cytokinesis and reveals novel mechanisms by which Neks regulate late mitosis.

Abstract

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.