RanGTP regulates the augmin complex

Kraus, Jodi; Travis, Sophie M; King, Matthew R.; Petry, Sabine

doi:10.1101/2022.12.23.521824

Cited by 2 publications

(2 citation statements)

References 67 publications

(100 reference statements)

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“…In agreement with our findings, a recent preprint identified two NLS motifs in the HAUS8 subunit of Xenopus augmin, one of which does not exist in human HAUS8 (Kraus et al 2022). These motifs in the Xenopus protein were also shown to be responsible, at least in part, for importin/Ran-GTP-dependent regulation of the binding of Xenopus augmin to microtubules.…”

Section: Discussionsupporting

confidence: 93%

“…These motifs in the Xenopus protein were also shown to be responsible, at least in part, for importin/Ran-GTP-dependent regulation of the binding of Xenopus augmin to microtubules. Therefore, the basic principle of direct importin/Ran-GTP regulation of the HAUS complex appears to be conserved between human and Xenopus , even if details of the NLS motifs may differ, which could explain why, in contrast to the human HAUS complex, microtubule binding of the Xenopus HAUS complex could not be completely blocked by importins (Kraus et al 2022).…”

Section: Discussionmentioning

confidence: 99%

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

Ustinova

Ruhnow

Gili

et al. 2023

Preprint

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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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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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

Ustinova

Ruhnow

Gili

et al. 2023

Preprint

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Acentrosomal spindles assemble from branching microtubule nucleation near chromosomes in Xenopus laevis egg extract

et al. 2023

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Microtubules are generated at centrosomes, chromosomes, and within spindles during cell division. Whereas microtubule nucleation at the centrosome is well characterized, much remains unknown about where, when, and how microtubules are nucleated at chromosomes. To address these questions, we reconstitute microtubule nucleation from purified chromosomes in meiotic Xenopus egg extract and find that chromosomes alone can form spindles. We visualize microtubule nucleation near chromosomes using total internal reflection fluorescence microscopy to find that this occurs through branching microtubule nucleation. By inhibiting molecular motors, we find that the organization of the resultant polar branched networks is consistent with a theoretical model where the effectors for branching nucleation are released by chromosomes, forming a concentration gradient that spatially biases branching microtbule nucleation. In the presence of motors, these branched networks are ultimately organized into functional spindles, where the number of emergent spindle poles scales with the number of chromosomes and total chromatin area.

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RanGTP regulates the augmin complex

Cited by 2 publications

References 67 publications

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

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

Acentrosomal spindles assemble from branching microtubule nucleation near chromosomes in Xenopus laevis egg extract

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