A Complex of Kif18b and MCAK Promotes Microtubule Depolymerization and Is Negatively Regulated by Aurora Kinases

• Published in: Current biology Vol. 21; no. 16; pp. 1356 - 1365
• Main Authors: Tanenbaum, Marvin E., Macurek, Libor, van der Vaart, Babet, Galli, Matilde, Akhmanova, Anna, Medema, René H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 23-08-2011
• Subjects: Aurora Kinases; binding proteins; Cell Line; Cysteine Proteinase Inhibitors - metabolism; depolymerization; Humans; interphase; kinases; Kinesin - genetics; Kinesin - metabolism; Leupeptins - metabolism; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; mitosis; Mitosis - physiology; nuclear membrane; phosphorylation; Protein Binding; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; RNA, Small Interfering - metabolism
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2011.07.017

Spindle assembly requires tight control of microtubule (MT) dynamics. This is dependent on a variety of MT binding proteins and their upstream regulators. The Aurora kinases have several well-described functions during cell division, but it remains unclear whether they control global spindle microtubule dynamics.
Here, we find that simultaneous inhibition of Aurora A and B results in a dramatic decrease in spindle MT stability, and we identify the uncharacterized kinesin-8 Kif18b as a mediator of this effect. In interphase, Kif18b is nuclear, but upon nuclear envelope breakdown, Kif18b binds to astral MT plus ends through an interaction with EB1. Surprisingly, Kif18b also binds to the kinesin-13 motor MCAK, and this interaction is required for robust MT depolymerization. Furthermore, the Kif18b-MCAK interaction is negatively regulated by Aurora kinases through phosphorylation of MCAK, indicating that Aurora kinases regulate MT plus-end stability in mitosis through control of Kif18b-MCAK complex formation.
Together, these results uncover a novel role for Aurora kinases in regulating spindle MT dynamics through Kif18b-MCAK and suggest that the Kif18b-MCAK complex constitutes the major MT plus-end depolymerizing activity in mitotic cells.
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► Kif18b is a MT plus-end tracker that preferentially localizes to astral MT plus ends ► Kif18b requires binding to EB1 and its motor activity for plus-end accumulation ► Kif18b binds to MCAK and acts through MCAK to promote MT destabilization ► Aurora kinases regulate Kif18b-MCAK complex formation through phosphorylation of MCAK