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ABL1 regulates spindle orientation in adherent cells and mammalian skin

Author

Listed:
  • Shigeru Matsumura

    (Institute for Virus Research, Kyoto University)

  • Mayumi Hamasaki

    (Institute for Virus Research, Kyoto University
    Graduate School of Biostudies, Kyoto University)

  • Takuya Yamamoto

    (Center for iPS Cell Research and Application (CiRA), Kyoto University, Sakyo-ku
    Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo-ku
    CREST, Japan Science and Technology Agency, 4-1-8 Honcho)

  • Miki Ebisuya

    (CREST, Japan Science and Technology Agency, 4-1-8 Honcho
    International Young Scientists Career Development Organization, Career-Path Promotion Unit for Young Life Scientists, Kyoto University)

  • Mizuho Sato

    (Graduate School of Biological Sciences, Nara Institute of Science and Technology)

  • Eisuke Nishida

    (CREST, Japan Science and Technology Agency, 4-1-8 Honcho
    Graduate School of Biostudies, Kyoto University)

  • Fumiko Toyoshima

    (Institute for Virus Research, Kyoto University)

Abstract

Despite the growing evidence for the regulated spindle orientation in mammals, a systematic approach for identifying the responsible genes in mammalian cells has not been established. Here we perform a kinase-targeting RNAi screen in HeLa cells and identify ABL1 as a novel regulator of spindle orientation. Knockdown of ABL1 causes the cortical accumulation of Leu-Gly-Asn repeat-enriched-protein (LGN), an evolutionarily conserved regulator of spindle orientation. This results in the LGN-dependent spindle rotation and spindle misorientation. In vivo inactivation of ABL1 by a pharmacological inhibitor or by ablation of the abl1 gene causes spindle misorientation and LGN mislocalization in mouse epidermis. Furthermore, ABL1 directly phosphorylates NuMA, a binding partner of LGN, on tyrosine 1774. This phosphorylation maintains the cortical localization of NuMA during metaphase, and ensures the LGN/NuMA-dependent spindle orientation control. This study provides a novel approach to identify genes regulating spindle orientation in mammals and uncovers new signalling pathways for this mechanism.

Suggested Citation

  • Shigeru Matsumura & Mayumi Hamasaki & Takuya Yamamoto & Miki Ebisuya & Mizuho Sato & Eisuke Nishida & Fumiko Toyoshima, 2012. "ABL1 regulates spindle orientation in adherent cells and mammalian skin," Nature Communications, Nature, vol. 3(1), pages 1-10, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1634
    DOI: 10.1038/ncomms1634
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    Cited by:

    1. Maria Fankhaenel & Farahnaz S. Golestan Hashemi & Larissa Mourao & Emily Lucas & Manal M. Hosawi & Paul Skipp & Xavier Morin & Colinda L.G.J. Scheele & Salah Elias, 2023. "Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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