Department of Molecular, Cell and Cancer Biology
Cancer Biology | Cell Biology | Developmental Biology | Molecular Biology
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-beta 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.
Rights and Permissions
Citation: Nat Commun. 2016 Mar 10;7:10972. doi: 10.1038/ncomms10972. Link to article on publisher's site
Cell signalling, Myosin, Proteases
Orme, Mariam H.; Tare, Meghana; Bergmann, Andreas; and Meier, Pascal, "The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles" (2016). Molecular, Cell and Cancer Biology Publications. 64.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.