Potent microtubule-depolymerizing activity of a mitotic Kif18b–MCAK–EB network

McHugh, T., and Welburn, J.P.I.

J Cell Sci (2023) 136 (5): jcs260144

Using in vitro reconstitution and cell biology, we demonstrated that kinesin motors Kif18b and MCAK and plus-end tracking protein EB3 act in an integrated manner to promote microtubule depolymerization during mitosis. We found that Kif18b can transport EB3 and MCAK increasing their accumulation to microtubule plus ends through multivalent weak interactions. At microtubule ends the complex induces microtubule catastrophe, efficiently shortening microtubules, which essential for correct spindle orientation during cell division.

Summary of Paper by Lori Koch

During cell division, dynamic protein fibres called microtubules hold the replicated chromosomes in the centre of the cell before they are pulled apart and into the two daughter cells. In order for chromosomes to be segregated properly, microtubules need to be precisely regulated so that they are the right length and have the right dynamic properties so that chromosomes are actually pulled around the cell. A protein enzyme called MCAK causes microtubule catastrophe, an event where the end of the microtubule depolymerizes and shrinks. In their recent study published in the Journal of Cell Science, postdoctoral scientist Toni McHugh in Julie Welburn’s group investigated the relationship between the microtubule motor protein Kif18b, MCAK, and the microtubule end-binding factor EB3. After finding that Kif18b was required for proper localization of MCAK to the microtubule tips in cells, they investigated their activity on microtubules in vitro using total internal fluorescence microscopy (TIRF), a technique that enables observation of single molecules. They found that MCAK moved along with Kif18b motors on microtubules and that MCAK, Kif18b, and EB3 tended to accumulate together at microtubule plus ends. By analyzing shorter forms of these molecules, they found that the N-terminus of MCAK interacts with Kif18b, which moves this enzyme cargo along microtubules. When they investigated the effect of these molecules on dynamic microtubules, they found that adding MCAK, Kif18b, and EB3 to microtubules together increased the frequency of catastrophe and decreased microtubule length more drastically than only adding two out of the three factors. Together, their work suggests that the motor protein Kif18b transports MCAK to microtubule plus ends where they form a functional network with the end-binding protein EB3. Kif18b stabilizes microtubule ends while MCAK promotes catastrophe and overall the right balance must be maintained so that the microtubules are long and dynamic enough to move chromosomes.

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