Coordinated control of adiposity and growth by anti-anabolic kinase ERK7.

ABSTRACT

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.