TY - JOUR
T1 - The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles
AU - Orme, Mariam H.
AU - Liccardi, Gianmaria
AU - Moderau, Nina
AU - Feltham, Rebecca
AU - Wicky-John, Sidonie
AU - Tenev, Tencho
AU - Aram, Lior
AU - Wilson, Rebecca
AU - Bianchi, Katiuscia
AU - Morris, Otto
AU - Domingues, Celia Monteiro
AU - Robertson, David
AU - Tare, Meghana
AU - Wepf, Alexander
AU - Williams, David
AU - Bergmann, Andreas
AU - Gstaiger, Matthias
AU - Arama, Eli
AU - Ribeiro, Paulo S.
AU - Meier, Pascal
PY - 2016/3/10
Y1 - 2016/3/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84960904302&partnerID=8YFLogxK
U2 - 10.1038/ncomms10972
DO - 10.1038/ncomms10972
M3 - Article
SN - 2041-1723
VL - 7
JO - Nature Communications
JF - Nature Communications
M1 - 10972
ER -