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

Reijo Käkelä,Krista Kokki,Ying Liu,Hanna Ruhanen,Kiran Hasygar,Josef Gullmets,Onur Deniz,Riikka Hynynen,Ville Hietakangas

doi:10.15252/embr.201949602

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.

Highlights

Animals live in changing nutrient landscape and are competing on limited nutrient resources
We report that an atypical MAP kinase ERK7 inhibits lipid storage and cell growth in the Drosophila fat body
ERK7 regulates the subcellular localization of the chromatin-binding protein PWP1 and inhibits the expression of the transcription factor, Sugarbabe

Summary

Introduction

Animals live in changing nutrient landscape and are competing on limited nutrient resources. The fat body (functional counterpart of mammalian liver and adipose tissue) has emerged as a key coordinator of growth signaling in Drosophila (Boulan et al, 2015) along with its essential role as a lipid synthesis and storage organ (Heier & Kuhnlein, 2018). It is a signaling hub for nutrient-dependent homeostatic control. Drosophila AMPK is necessary for larval growth and adiposity by affecting visceral muscle function and food intake, rather than acting tissue autonomously in the fat body (Bland et al, 2010) This implies that other anti-anabolic kinases might be involved in fat body-mediated homeostatic control during the growth phase of the animal

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