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The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles

Author

Listed:
  • Mariam H. Orme

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

  • Gianmaria Liccardi

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

  • Nina Moderau

    (John Vane Science Centre, Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK)

  • Rebecca Feltham

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

  • Sidonie Wicky-John

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

  • Tencho Tenev

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

  • Lior Aram

    (Weizmann Institute of Science)

  • Rebecca Wilson

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

  • Katiuscia Bianchi

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

  • Otto Morris

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

  • Celia Monteiro Domingues

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

  • David Robertson

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

  • Meghana Tare

    (University of Massachusetts Medical School)

  • Alexander Wepf

    (ETH, Institute for Molecular Systems Biology)

  • David Williams

    (UCLA David Geffen School of Medicine)

  • Andreas Bergmann

    (University of Massachusetts Medical School)

  • Matthias Gstaiger

    (ETH, Institute for Molecular Systems Biology)

  • Eli Arama

    (Weizmann Institute of Science)

  • Paulo S. Ribeiro

    (John Vane Science Centre, Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK)

  • Pascal Meier

    (Chester Beatty Laboratories, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research)

Abstract

Caspases provide vital links in non-apoptotic regulatory networks controlling inflammation, compensatory proliferation, morphology and cell migration. How caspases are activated under non-apoptotic conditions and process a selective set of substrates without killing the cell remain enigmatic. Here we find that the Drosophila unconventional myosin CRINKLED (CK) selectively interacts with the initiator caspase DRONC and regulates some of its non-apoptotic functions. Loss of CK in the arista, border cells or proneural clusters of the wing imaginal discs affects DRONC-dependent patterning. Our data indicate that CK acts as substrate adaptor, recruiting SHAGGY46/GSK3-β to DRONC, thereby facilitating caspase-mediated cleavage and localized modulation of kinase activity. Similarly, the mammalian CK counterpart, MYO7A, binds to and impinges on CASPASE-8, revealing a new regulatory axis affecting receptor interacting protein kinase-1 (RIPK1)>CASPASE-8 signalling. Together, our results expose a conserved role for unconventional myosins in transducing caspase-dependent regulation of kinases, allowing them to take part in specific signalling events.

Suggested Citation

  • Mariam H. Orme & Gianmaria Liccardi & Nina Moderau & Rebecca Feltham & Sidonie Wicky-John & Tencho Tenev & Lior Aram & Rebecca Wilson & Katiuscia Bianchi & Otto Morris & Celia Monteiro Domingues & Dav, 2016. "The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10972
    DOI: 10.1038/ncomms10972
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