The integrated stress response regulates BMP signalling through effects on translation

• DOI: 10.1186/s12915-018-0503-x
• Publication Date: 2018-04-04T03:38:10Z
• Authors: Elke Malzer; Caia S. Dominicus; Joseph E. Chambers; Jennifer A. Dickens; Souradip Mookerjee; Stefan J. Marciniak
• Keywords: Integrated stress response; Signalling

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