Drosophila EYA regulates the immune response against DNA through an evolutionarily conserved threonine phosphatase motif.
Innate immune responses against DNA are essential to counter both pathogen infections and tissue damages. Mammalian EYAs were recently shown to play a role in regulating the innate immune responses against DNA. Here, we demonstrate that the unique Drosophila eya gene is also involved in the response specific to DNA. Haploinsufficiency of eya in mutants deficient for lysosomal DNase activity (DNaseII) reduces antimicrobial peptide gene expression, a hallmark for immune responses in flies. Like the mammalian orthologues, Drosophila EYA features a N-terminal threonine and C-terminal tyrosine phosphatase domain. Through the generation of a series of mutant EYA fly strains, we show that the threonine phosphatase domain, but not the tyrosine phosphatase domain, is responsible for the innate immune response against DNA. A similar role for the threonine phosphatase domain in mammalian EYA4 had been surmised on the basis of in vitro studies. Furthermore EYA associates with IKKβ and full-length RELISH, and the induction of the IMD pathway-dependent antimicrobial peptide gene is independent of SO. Our data provide the first in vivo demonstration for the immune function of EYA and point to their conserved immune function in response to endogenous DNA, throughout evolution.
INSERM Equipe Avenir, CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
Xi
X
Liu
Teruyuki
T
Sano
Yongsheng
Y
Guan
Shigekazu
S
Nagata
Jules A
JA
Hoffmann
Hidehiro
H
Fukuyama
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism
D029721:Drosophila Proteins; D005136:Eye Proteins; D014157:Transcription Factors; C092694:eya protein, Drosophila; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II; D010749:Phosphoprotein Phosphatases