Eiger and its receptor, Wengen, comprise a TNF-like system in Drosophila.
In mammals, members of the tumor necrosis factor (TNF) family play an important role in the regulation of cellular proliferation, differentiation and programmed cell death. We describe isolation and characterization of an orthologous ligand/receptor axis in Drosophila. The ligand, designated Eiger, is a type II membrane glycosylated protein, which can be cleaved at residue 145 and released from the cell surface as a soluble factor, thereby representing the first potential cytokine to be described in Drosophila. Eiger exists in two alternatively spliced isoforms, Eiger long (Eiger-L) and Eiger short (Eiger-s), both of which are expressed throughout development and in the adult. We also describe the isolation and characterization of a novel Drosophila member of the TNF receptor family, designated Wengen, which is a type I membrane protein that can physically interact with the recently described TRAF2 homolog dTRAF2. Both Eiger and Wengen are expressed in distinctive patterns during embryogenesis and Eiger is responsive to genotoxic stress. Forced expression of Eiger-L, Eiger-s or Wengen, caused apoptotic cell death which could be rescued by caspase inhibitors or the JNK phosphatase Puckered. In addition, Eiger-induced cell killing was attenuated by RNAi-mediated suppression of Wengen. Our results illustrate that Eiger and Wengen represent proximal components of an evolutionarily conserved TNF-like signaling pathway in Drosophila.
Kauppila
Saila
S
Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-8593, USA.
Maaty
Walid S A
WS
Chen
Po
P
Tomar
Raghuvir S
RS
Eby
Michael T
MT
Chapo
Joe
J
Chew
Sukit
S
Rathore
Nisha
N
Zachariah
Sunny
S
Sinha
Suwan K
SK
Abrams
John M
JM
Chaudhary
Preet M
PM
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D018076:DNA, Complementary / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing / Q000187:drug effects; D006031:Glycosylation; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000502:physiology; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism; D016372:RNA, Antisense / Q000502:physiology; D012330:RNA, Double-Stranded / Q000494:pharmacology; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013045:Species Specificity; D047992:TNF Receptor-Associated Factor 2; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry
D018076:DNA, Complementary; D029721:Drosophila Proteins; D008565:Membrane Proteins; D011506:Proteins; D016372:RNA, Antisense; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; C464573:egr protein, Drosophila; C464933:wgn protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C110854:puc protein, Drosophila; D010749:Phosphoprotein Phosphatases