Wengen, a member of the Drosophila tumor necrosis factor receptor superfamily, is required for Eiger signaling.
We identified Wengen, the first member of the Drosophila tumor necrosis factor receptor (TNFR) superfamily. Wengen is a type III membrane protein with conserved cysteine-rich residues (TNFR homology domain) in the extracellular domain, a hallmark of the TNFR superfamily. wengen mRNA is expressed at all stages of Drosophila development. The small-eye phenotype caused by an eye-specific overexpression of a Drosophila TNF superfamily ligand, Eiger, was dramatically suppressed by down-regulation of Wengen using RNA interference. In addition, Wengen and Eiger physically interacted with each other through their TNFR homology domain and TNF homology domain, respectively. These results suggest that Wengen can act as a component of a functional receptor for Eiger. Our identification of Wengen and further genetic analysis should provide increased understanding of the evolutionarily conserved roles of TNF/TNFR superfamily proteins in normal development, as well as in some pathophysiological conditions.
Kanda
Hiroshi
H
Laboratory for Cell Recovery Mechanisms, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Igaki
Tatsushi
T
Kanuka
Hirotaka
H
Yagi
Takeshi
T
Miura
Masayuki
M
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D008024:Ligands; D008565:Membrane Proteins / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010641:Phenotype; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018076:DNA, Complementary; D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C464573:egr protein, Drosophila; C464933:wgn protein, Drosophila