4.7 Article

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

Journal

JOURNAL OF CELL BIOLOGY
Volume 216, Issue 8, Pages 2339-2354

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201512055

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Funding

  1. National Institutes of Health [P20-GM103413, S10-OD016212, R01-CA155260, R35-GM119455]
  2. Dartmouth College Molecular and Cellular Biology training grant [T32-GM008704]

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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 post-translational 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.

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