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

Open access
Author
Orme, Mariam H.
Liccardi, Gianmaria
Moderau, Nina
Feltham, Rebecca
Wicky-John, Sidonie
Tenev, Tencho
Aram, Lior
Wilson, Rebecca
Bianchi, Katiuscia
Morris, Otto
Monteiro Domingues, Celia
Robertson, David
Tare, Meghana
Wepf, Alexander
Williams, David
Bergmann, Andreas
Gstaiger, Matthias
Arama, Eli
Ribeiro, Paulo S.
Meier, Pascal
Date
2016Type
- Journal Article
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 Show more
Permanent link
https://doi.org/10.3929/ethz-b-000114437Publication status
publishedJournal / series
Nature CommunicationsVolume
Pages / Article No.
Publisher
Nature Publishing GroupMore
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