Genetic evidence of a redox-dependent systemic wound response via Hayan protease-phenoloxidase system in Drosophila.
Systemic wound response (SWR) through intertissue communication in response to local wounds is an essential biological phenomenon that occurs in all multicellular organisms from plants to animals. However, our understanding of SWR has been greatly hampered by the complexity of wound signalling communication operating within the context of an entire organism. Here, we show genetic evidence of a redox-dependent SWR from the wound site to remote tissues by identifying critical genetic determinants of SWR. Local wounds in the integument rapidly induce activation of a novel circulating haemolymph serine protease, Hayan, which in turn converts pro-phenoloxidase (PPO) to phenoloxidase (PO), an active form of melanin-forming enzyme. The Haemolymph Hayan-PO cascade is required for redox-dependent activation of the c-Jun N-terminal kinase (JNK)-dependent cytoprotective program in neuronal tissues, thereby achieving organism level of homeostasis to resist local physical trauma. These results imply that the PO-activating enzyme cascade, which is a prominent defense system in humoral innate immunity, also mediates redox-dependent SWR, providing a novel link between wound response and the nervous system.
School of Biological Sciences, Seoul National University and National Creative Research Initiative Center for Symbiosystem, Seoul, Republic of Korea.
Hyuck-Jin
HJ
Nam
In-Hwan
IH
Jang
Hyejin
H
You
Kyung-Ah
KA
Lee
Won-Jae
WJ
Lee
D000818:Animals; D004330:Drosophila / Q000201:enzymology* / Q000502:physiology; D006458:Hemolymph / Q000201:enzymology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010084:Oxidation-Reduction; D057057:Serine Proteases / Q000378:metabolism*; D014945:Wound Healing
D014442:Monophenol Monooxygenase; D048031:JNK Mitogen-Activated Protein Kinases; D057057:Serine Proteases