Journal
EMBO REPORTS
Volume 22, Issue 2, Pages -Publisher
WILEY
DOI: 10.15252/embr.201949602
Keywords
growth; lipid metabolism; nutrient sensing; signaling
Categories
Funding
- Hi-Fly core facility
- Academy of Finland [286767, 312439]
- Sigrid Juselius Foundation
- Novo Nordisk Foundation [NNF16OC0021460, NNF18OC0034406, NNF19OC0057478]
- Diabetes Research Foundation
- Integrative Life Science Doctoral Program
- Finnish Academy of Science and Letters
- Biomedicum Helsinki Foundation
- Ella and Georg Ehrnrooth Foundation
- Cancer Society of Finland
- Academy of Finland (AKA) [312439, 286767, 312439, 286767] Funding Source: Academy of Finland (AKA)
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Energy storage and growth in animals are coordinated in response to nutrient status, with nutrient-regulated signaling pathways controlling these processes. ERK7 has been identified as an atypical MAP kinase inhibitor of adiposity and growth in Drosophila, with its mutant larvae showing increased lipid stores and accelerated growth. Moreover, ERK7 expression is elevated during fasting conditions, and ERK7 mutant larvae display impaired survival during nutrient deprivation.
Energy storage and growth are coordinated in response to nutrient status of animals. How nutrient-regulated signaling pathways control these processes in vivo remains insufficiently understood. Here, we establish an atypical MAP kinase, ERK7, as an inhibitor of adiposity and growth in Drosophila. ERK7 mutant larvae display elevated triacylglycerol (TAG) stores and accelerated growth rate, while overexpressed ERK7 is sufficient to inhibit lipid storage and growth. ERK7 expression is elevated upon fasting and ERK7 mutant larvae display impaired survival during nutrient deprivation. ERK7 acts in the fat body, the insect counterpart of liver and adipose tissue, where it controls the subcellular localization of chromatin-binding protein PWP1, a growth-promoting downstream effector of mTOR. PWP1 maintains the expression of sugarbabe, encoding a lipogenic Gli-similar family transcription factor. Both PWP1 and Sugarbabe are necessary for the increased growth and adiposity phenotypes of ERK7 loss-of-function animals. In conclusion, ERK7 is an anti-anabolic kinase that inhibits lipid storage and growth while promoting survival on fasting conditions.
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