A serine protease zymogen functions as a pattern-recognition receptor for lipopolysaccharides.
Bacterial lipopolysaccharide (LPS)-induced exocytosis of granular hemocytes is a key component of the horseshoe crab's innate immunity to infectious microorganisms; stimulation by LPS induces the secretion of various defense molecules from the granular hemocytes. Using a previously uncharacterized assay for exocytosis, we clearly show that hemocytes respond only to LPS and not to other pathogen-associated molecular patterns, such as beta-1,3-glucans and peptidoglycans. Furthermore, we show that a granular protein called factor C, an LPS-recognizing serine protease zymogen that initiates the hemolymph coagulation cascade, also exists on the hemocyte surface as a biosensor for LPS. Our data demonstrate that the proteolytic activity of factor C is both necessary and sufficient to trigger exocytosis through a heterotrimeric GTP-binding protein-mediating signaling pathway. Exocytosis of hemocytes was not induced by thrombin, but it was induced by hexapeptides corresponding to the tethered ligands of protease-activated G protein-coupled receptors (PARs). This finding suggested the presence of a PAR-like receptor on the hemocyte surface. We conclude that the serine protease zymogen on the hemocyte surface functions as a pattern-recognition protein for LPS.
Ariki
Shigeru
S
Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
Koori
Kumiko
K
Osaki
Tsukasa
T
Motoyama
Kiyohito
K
Inamori
Kei-ichiro
K
Kawabata
Shun-ichiro
S
D004797:Enzyme-Linked Immunosorbent Assay; D005089:Exocytosis; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000378:metabolism; D006868:Hydrolysis; D008070:Lipopolysaccharides / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*
D008070:Lipopolysaccharides; D012697:Serine Endopeptidases; D019204:GTP-Binding Proteins