The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles.
Date
2016-03-10Author
Orme, MH
Liccardi, G
Moderau, N
Feltham, R
Wicky-John, S
Tenev, T
Aram, L
Wilson, R
Bianchi, K
Morris, O
Monteiro Domingues, C
Robertson, D
Tare, M
Wepf, A
Williams, D
Bergmann, A
Gstaiger, M
Arama, E
Ribeiro, PS
Meier, P
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Cell Line, Tumor
NIH 3T3 Cells
Animals
Humans
Mice
Drosophila melanogaster
Myosins
Caspases
Glycogen Synthase Kinase 3
Drosophila Proteins
Microscopy, Confocal
Flow Cytometry
Immunoprecipitation
Signal Transduction
Caspase 8
Receptor-Interacting Protein Serine-Threonine Kinases
Wings, Animal
Glycogen Synthase Kinase 3 beta
Myosin VIIa
Research team
Cell Death and Immunity
Target Discovery & Apoptosis
Language
eng
Date accepted
2016-02-05
License start date
2016-03-10
Citation
Nature communications, 2016, 7 pp. 10972 - ?
Publisher
NATURE PUBLISHING GROUP