Format

Send to

Choose Destination
Cell. 2013 Oct 10;155(2):435-47. doi: 10.1016/j.cell.2013.09.007. Epub 2013 Sep 26.

MEF2 is an in vivo immune-metabolic switch.

Author information

1
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.

Abstract

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.

Comment in

PMID:
24075010
PMCID:
PMC3807682
DOI:
10.1016/j.cell.2013.09.007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center