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

Mariam H. Orme, Gianmaria Liccardi, Nina Moderau, Rebecca Feltham, Sidonie Wicky-John, Tencho Tenev, Lior Aram, Rebecca Wilson, Katiuscia Bianchi, Otto Morris, Celia Monteiro Domingues, David Robertson, Meghana Tare, Alexander Wepf, David Williams, Andreas Bergmann, Matthias Gstaiger, Eli Arama, Paulo S. Ribeiro, Pascal Meier

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

ملخص

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.
اللغة الأصليةالإنجليزيّة
رقم المقال10972
الصفحات (من إلى)10972
عدد الصفحات12
دوريةNature Communications
مستوى الصوت7
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - مارس 2016

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