1. Research Institute of Molecular Pathology, Dr. Bohrgasse 7, A-1030 Vienna, Austria
2. Max-Planck-Institute für Biochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany

Correspondence to: Michael Glotzer¹ Correspondence and requests for materials should be addressed to M.G. (Email: mglotzer@imp.univie.ac.at).

Abstract

The bipolar mitotic spindle is responsible for segregating sister chromatids at anaphase. Microtubule motor proteins generate spindle bipolarity and enable the spindle to perform mechanical work¹. A major change in spindle architecture occurs at anaphase onset when central spindle assembly begins. This structure regulates the initiation of cytokinesis and is essential for its completion². Central spindle assembly requires the centralspindlin complex composed of the Caenorhabditis elegans ZEN-4 (mammalian orthologue MKLP1) kinesin-like protein and the Rho family GAP CYK-4 (MgcRacGAP). Here we describe a regulatory mechanism that controls the timing of central spindle assembly. The mitotic kinase Cdk1/cyclin B phosphorylates the motor domain of ZEN-4 on a conserved site within a basic amino-terminal extension characteristic of the MKLP1 subfamily. Phosphorylation by Cdk1 diminishes the motor activity of ZEN-4 by reducing its affinity for microtubules. Preventing Cdk1 phosphorylation of ZEN-4/MKLP1 causes enhanced metaphase spindle localization and defects in chromosome segregation. Thus, phosphoregulation of the motor domain of MKLP1 kinesin ensures that central spindle assembly occurs at the appropriate time in the cell cycle and maintains genomic stability.

1. Research Institute of Molecular Pathology, Dr. Bohrgasse 7, A-1030 Vienna, Austria
2. Max-Planck-Institute für Biochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany

Correspondence to: Michael Glotzer¹ Correspondence and requests for materials should be addressed to M.G. (Email: mglotzer@imp.univie.ac.at).

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