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

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Embargo End Date

ICR Authors

Morris, Otto
 Meier, Pascal

Authors

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

Document Type

Journal Article

Date

2016-03-10

Date Accepted

2016-02-05

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.

Citation

Nature communications, 2016, 7 pp. 10972 - ?

DOI

10.1038/ncomms10972

URI

https://repository.icr.ac.uk/handle/internal/93

Rights

https://creativecommons.org/licenses/by/4.0

Source Title

Publisher

NATURE PUBLISHING GROUP

ISSN

2041-1723

eISSN

2041-1723

Collections

Breast Cancer Research
Cancer Therapeutics

Research Team

Cell Death and Immunity
Target Discovery & Apoptosis

Notes