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Malzer, E., Dominicus, C.S., Chambers, J.E., Dickens, J.A., Mookerjee, S., Marciniak, S.J. (2018). The integrated stress response regulates BMP signalling through effects on translation.  BMC Biol. 16(1): 34.
FlyBase ID
FBrf0238534
Publication Type
Research paper
Abstract

Developmental pathways must be responsive to the environment. Phosphorylation of eIF2α enables a family of stress-sensing kinases to trigger the integrated stress response (ISR), which has pro-survival and developmental consequences. Bone morphogenetic proteins (BMPs) regulate multiple developmental processes in organisms from insects to mammals. Here we show in Drosophila that GCN2 antagonises BMP signalling through direct effects on translation and indirectly via the transcription factor crc (dATF4). Expression of a constitutively active GCN2 or loss of the eIF2α phosphatase dPPP1R15 impairs developmental BMP signalling in flies. In cells, inhibition of translation by GCN2 blocks downstream BMP signalling. Moreover, loss of d4E-BP, a target of crc, augments BMP signalling in vitro and rescues tissue development in vivo. These results identify a novel mechanism by which the ISR modulates BMP signalling during development.

PubMed ID
PubMed Central ID
PMC5881181 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    BMC Biol.
    Title
    BMC Biology
    ISBN/ISSN
    1741-7007
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