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

Ustinova, Kseniya; Ruhnow, Felix; Gili, Maria; Surrey, Thomas

doi:http://dx.doi.org/10.1242/jcs.261096

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

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Ustinova K, Ruhnow F, Gili M, Surrey T. Microtubule binding of the human augmin complex is directly controlled by importins and Ran-GTP. J Cell Sci. 2023 Jun 15;136(12):jcs261096. DOI: 10.1242/jcs.261096

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 local stimulation of branched microtubule nucleation around chromosomes, which is mediated by the augmin complex (composed of the eight subunits HAUS1-HAUS8), a process that is crucially 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 augmin complex. We demonstrate that importins directly bind to augmin, which prevents augmin from binding to microtubules. Ran-GTP relieves this inhibition. Therefore, the augmin 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.