Microtubule binding of the human HAUS complex is directly controlled by importins and Ran-GTP

Ustinova, K.; Ruhnow, F.; Gili, M.; Surrey, T.

doi:10.1101/2023.02.19.529112

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bioRxiv · 10.1101/2023.02.19.529112

Microtubule binding of the human HAUS complex is directly controlled by importins and Ran-GTP

Ustinova, K.·Ruhnow, F.·Gili, M.·Surrey, T.

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Abstract

Mitotic spindle assembly during cell division is a highly regulated process. Ran-GTP produced around chromosomes controls the activity of a multitude of spindle assembly factors by releasing them from inhibitory interaction with importins. A major consequence of Ran-GTP regulation is the stimulation of local microtubule nucleation around chromosomes via augmin/HAUS-mediated branched microtubule nucleation, a process that is critically important for correct spindle assembly. However, augmin is not known to be a direct target of the Ran-GTP pathway, raising the question of how its activity is controlled. Here we present the in vitro reconstitution of Ran-GTP-regulated microtubule binding of the human HAUS complex. We demonstrate that importins directly bind to the HAUS complex, which prevents HAUS from binding to microtubules. Ran-GTP relieves this inhibition. Therefore, the HAUS complex is a direct target of the Ran-GTP pathway, suggesting that branching microtubule nucleation is directly regulated by the Ran-GTP gradient around chromosomes in dividing cells.

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Ustinova, K., Ruhnow, F., Gili, M., Surrey, T.. 2023-02-20. Microtubule binding of the human HAUS complex is directly controlled by importins and Ran-GTP. https://doi.org/10.1101/2023.02.19.529112

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