Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger.
The prophenoloxidase-activating cascade is a key component of arthropod immunity. Drosophila prophenoloxidase is stored in crystal cells, a specialized class of blood cells from which it is released through cell rupture. Within minutes after bleeding, prophenoloxidase is activated leading to visible melanization of the clot matrix. Using crystal cell rupture and melanization as readouts to screen mutants in signal transduction pathways, we show that prophenoloxidase release requires Jun N-terminal kinase, small Rho GTPases and Eiger, the Drosophila homolog of tumor necrosis factor. We also provide evidence that in addition to microbial products, endogenous signals from dying hemocytes contribute to triggering and/or assembly of the prophenoloxidase-activating cascade, and that this process can be inhibited in vitro and in vivo using the viral apoptotic inhibitor p35. Our results provide a more comprehensive view of immune signal transduction pathways, with implications for immune reactions where cell death is used as a terminal mode of cell activation.
Bidla
Gawa
G
Department of Molecular Biology and Functional Genomics, University of Stockholm, Svante Arrheniusväg 16-18, SE 10691 Stockholm, Sweden.
Dushay
Mitchell S
MS
Theopold
Ulrich
U
D000818:Animals; D017209:Apoptosis; D004330:Drosophila / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D004789:Enzyme Activation; D006434:Hemocytes / Q000201:enzymology*; D006458:Hemolymph / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology*; D014442:Monophenol Monooxygenase / Q000097:blood
D029721:Drosophila Proteins; D008565:Membrane Proteins; C464573:egr protein, Drosophila; D014442:Monophenol Monooxygenase; D048031:JNK Mitogen-Activated Protein Kinases; D020559:Monomeric GTP-Binding Proteins