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The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation

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  • Hideki Yokoyama

    (Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Alliance
    European Molecular Biology Laboratory)

  • Birgit Koch

    (European Molecular Biology Laboratory)

  • Rudolf Walczak

    (European Molecular Biology Laboratory)

  • Fulya Ciray-Duygu

    (Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Alliance)

  • Juan Carlos González-Sánchez

    (Centre for Organismal Studies (COS))

  • Damien P. Devos

    (Centre for Organismal Studies (COS))

  • Iain W. Mattaj

    (European Molecular Biology Laboratory)

  • Oliver J. Gruss

    (Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Alliance)

Abstract

The GTP-bound form of the Ran GTPase (RanGTP), produced around chromosomes, drives nuclear envelope and nuclear pore complex (NPC) re-assembly after mitosis. The nucleoporin MEL-28/ELYS binds chromatin in a RanGTP-regulated manner and acts to seed NPC assembly. Here we show that, upon mitotic NPC disassembly, MEL-28 dissociates from chromatin and re-localizes to spindle microtubules and kinetochores. MEL-28 directly binds microtubules in a RanGTP-regulated way via its C-terminal chromatin-binding domain. Using Xenopus egg extracts, we demonstrate that MEL-28 is essential for RanGTP-dependent microtubule nucleation and spindle assembly, independent of its function in NPC assembly. Specifically, MEL-28 interacts with the γ-tubulin ring complex and recruits it to microtubule nucleation sites. Our data identify MEL-28 as a RanGTP target that functions throughout the cell cycle. Its cell cycle-dependent binding to chromatin or microtubules discriminates MEL-28 functions in interphase and mitosis, and ensures that spindle assembly occurs only after NPC breakdown.

Suggested Citation

  • Hideki Yokoyama & Birgit Koch & Rudolf Walczak & Fulya Ciray-Duygu & Juan Carlos González-Sánchez & Damien P. Devos & Iain W. Mattaj & Oliver J. Gruss, 2014. "The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation," Nature Communications, Nature, vol. 5(1), pages 1-9, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4270
    DOI: 10.1038/ncomms4270
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