Sung-Hee Kim, Carl Hashimoto, In-Hwan Jang, Sylvain Brun, Zakaria Kambris, Masaaki Ashida, Naoyuki Chosa, Hyuck-Jin Nam, Won-Jae Lee, Masanori Ochiai, Paul T. Brey, Bruno Lemaitre, Biochimie et Biologie Moléculaire des Insectes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Division of Molecular Life Science, Ewha Womans University, Seoul, EWHA Womans University (EWHA), Institute of Low-Temperature Science, Hokkaido University [Sapporo, Japan], Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Department of Cell Biology [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM)-Howard Hughes Medical Institute (HHMI), Laboratory of Innate Immunology, Institut Pasteur Korea - Institut Pasteur de Corée, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Korea Science and Engineering Foundation (R2-2000-000-26-0, R2-2001-000-35-0, and R2- 2002-000-58-0), the Center for Cell Signaling Research from the Ministry of Science and Technology of Korea, Institut Pasteur Korea, and an Ewha Womans University Grant. S.-H.K. and H.-J.N. were supported by the Brain Korea 21 project of the Korea Ministry of Education. I.-H.J. and P.T.B were supported by Institut Pasteur Paris. C.H. was supported by National Institutes of Health grant GM49370. M.A. was supported by the Japan Ministry of Education, Science and Culture (13143201) and the Mitsubishi Foundation, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Yale University School of Medicine-Howard Hughes Medical Institute (HHMI)
SummaryThe Toll receptor was originally identified as an indispensable molecule for Drosophila embryonic development and subsequently as an essential component of innate immunity from insects to humans. Although in Drosophila the Easter protease processes the pro-Spätzle protein to generate the Toll ligand during development, the identification of the protease responsible for pro-Spätzle processing during the immune response has remained elusive for a decade. Here, we report a protease, called Spätzle-processing enzyme (SPE), required for Toll-dependent antimicrobial response. Flies with reduced SPE expression show no noticeable pro-Spätzle processing and become highly susceptible to microbial infection. Furthermore, activated SPE can rescue ventral and lateral development in embryos lacking Easter, showing the functional homology between SPE and Easter. These results imply that a single ligand/receptor-mediated signaling event can be utilized for different biological processes, such as immunity and development, by recruiting similar ligand-processing proteases with distinct activation modes.