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

J Cell Biol. 2017 Aug 7;216(8):2339-2354. doi: 10.1083/jcb.201512055. Epub 2017 Jun 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Anaphase*
  • Chromatography, Affinity
  • Cytokinesis*
  • HeLa Cells
  • Humans
  • Hydrolysis
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kinesin / genetics
  • Kinesin / metabolism*
  • NIMA-Related Kinases / genetics
  • NIMA-Related Kinases / metabolism*
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA Interference
  • Signal Transduction
  • Spindle Apparatus / enzymology*
  • Tandem Mass Spectrometry
  • Time Factors
  • Transfection

Substances

  • Intracellular Signaling Peptides and Proteins
  • KIF20A protein, human
  • Oncogene Proteins
  • Adenosine Triphosphate
  • citron-kinase
  • NEK6 protein, human
  • NEK7 protein, human
  • NEK9 protein, human
  • NIMA-Related Kinases
  • Protein-Serine-Threonine Kinases
  • KIF14 protein, human
  • Kinesin