MEF2 is an in vivo immune-metabolic switch.
Infections disturb metabolic homeostasis in many contexts, but the underlying connections are not completely understood. To address this, we use paired genetic and computational screens in Drosophila to identify transcriptional regulators of immunity and pathology and their associated target genes and physiologies. We show that Mef2 is required in the fat body for anabolic function and the immune response. Using genetic and biochemical approaches, we find that MEF2 is phosphorylated at a conserved site in healthy flies and promotes expression of lipogenic and glycogenic enzymes. Upon infection, this phosphorylation is lost, and the activity of MEF2 changes--MEF2 now associates with the TATA binding protein to bind a distinct TATA box sequence and promote antimicrobial peptide expression. The loss of phosphorylated MEF2 contributes to loss of anabolic enzyme expression in Gram-negative bacterial infection. MEF2 is thus a critical transcriptional switch in the adult fat body between metabolism and immunity.
Centre for the Molecular and Cellular Biology of Inflammation and Peter Gorer Department of Immunobiology, King's College London School of Medicine, London SE1 1UL, UK; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Rebecca I
RI
Clark
Sharon W S
SW
Tan
Claire B
CB
Péan
Urmas
U
Roostalu
Valérie
V
Vivancos
Kévin
K
Bronda
Martina
M
Pilátová
Jingqi
J
Fu
David W
DW
Walker
Rebecca
R
Berdeaux
Frédéric
F
Geissmann
Marc S
MS
Dionne
D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans; D029721:Drosophila Proteins / Q000276:immunology / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D016972:Enterobacter cloacae; D005216:Fat Body / Q000378:metabolism; D005786:Gene Expression Regulation; D006003:Glycogen / Q000378:metabolism; D008660:Metabolism; D019910:Mycobacterium marinum; D018006:Myogenic Regulatory Factors / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D035181:TATA-Box Binding Protein / Q000378:metabolism
D029721:Drosophila Proteins; C499409:Mef2 protein, Drosophila; D018006:Myogenic Regulatory Factors; D035181:TATA-Box Binding Protein; D006003:Glycogen