


Shun-ichiro Kawabata | Last modified date:2022.04.27 |

Professor /
Division of Integrative Biology, Laboratory of Protein Sciences
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Homepage
https://kyushu-u.pure.elsevier.com/en/persons/shun-ichiro-kawabata
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http://www.biology.kyushu-u.ac.jp/%7Ebiopoly/
Molecular mechanisms of invertebrate innate immmunity .
Academic Degree
Ph. D.
Country of degree conferring institution (Overseas)
No
Field of Specialization
Biochemistry, Protein Chemistry, Protein Science, Enzymology (Proteases), Invertebrate innate immunity, lipid-protein interaction
Total Priod of education and research career in the foreign country
02years06months
Outline Activities
Innate immunity, which defends the host against infectious pathogens, is an ancient and ubiquitous immune system in both vertebrates and invertebrates. Each species employs a variety of environment-specific adaptations to ensure host defense, whereas a generalized recognition strategy against invading pathogens underlies the innate immune reaction. The innate immune system recognizes broadly conserved microbial cell wall components known as pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharides (LPS) of Gram-negative bacteria, peptidoglycans of Gram-positive bacteria, and β-1,3-D-glucans of fungi via pattern-recognition proteins. Innate immune systems in invertebrates consists of pathways that promote recognition of pathogen-associated macromolecules, hemolymph coagulation, phenoloxidase-mediated melanization, cell agglutination, antimicrobial activity, and phagocytosis. The horseshoe crab belongs to the class Merostomata and is phylogenetically more closely related to Arachnoidea than it is to Crustacea. Fossils of horseshoe crabs, such as Mesolimulus walchi and Limulus coffini, have been found in deposits from the Paleozoic era to the Cenozoic era in Europe and North America. Extant horseshoe crabs comprise four species, Limulus polyphemus, Tachypleus tridentatus, T. gigas, and Carcinoscorpius rotundicauda, each having a distinct geographic distribution; L. polyphemus is distributed along the east coast of North America, and the other three species are mainly distributed throughout Southeast Asia. In Japan, T. tridentatus inhabits coastal areas of the northern part of Kyushu Island as well as the Inland Sea. T. tridentatus has proven to be a suitable model system for the investigation of arthropod immunity, since, in addition to having a sophisticated innate immune system, it is relatively long-lived; the embryo molts four times within the fertilized egg, and after hatching it molts every year over 15 years to become a mature adult.
Primary stimulation of the horseshoe crab innate immune system by lipopolysaccharide (LPS) activates a network of responses to ensure host defense against invading pathogens. Granular hemocytes selectively respond to bacterial lipopolysaccharides (LPS) via a G protein-dependent exocytic pathway that critically depends on the proteolytic activity of the LPS-responsive coagulation factor C. In response to stimulation by LPS, the hemocyte secretes transglutaminase (TG) and several kinds of defense molecules, such as coagulation factors, lectins, antimicrobial peptides, and protein substrates for TG. LPS-induced hemocyte exocytosis is enhanced by a feedback mechanism in which the antimicrobial peptide tachyplesin serves as an endogenous mediator. The coagulation cascade triggered by LPS or β-1,3-D-glucans results in the formation of coagulin fibrils that are subsequently stabilized by TGase-dependent cross-linking. A cuticle-derived chitin-binding protein additionally forms a TGase-stabilized mesh at sites of injury. Invading pathogens are agglutinated by both hemocyte- and plasma-derived lectins. In addition, the proclotting enzyme and tachyplesin functionally convert hemocyanin to phenoloxidase. In the plasma, coagulation factor C acts an LPS-sensitive complement C3 convertase on the surface of Gram-negative bacteria. In this manner, LPS-induced hemocyte exocytosis leads not only to coagulation but also activates a sophisticated innate immune response network that coordinately effects pathogen recognition, prophenoloxidase activation, pathogen clearance, and TG-dependent wound healing. Recently, using molecular biological techniques of Drosophila, we analyze the molecular mechanism of host-commensal microbes cross-talk to maintain a buffered threshold required for immune tolerance against commensal microbes in the gut.Recently, we found that two types of fatty-acid: N-myristoylation and S-palmitoylation modify TG-A. TG-A is one of the two alternative splicing forms of TGs (A and B) and it control not only its localization on the plasma membrane through an unconventional secretory pathway, but also its secretion in response to external stimuli such as bacterial infection. Moreover, ultracentrifugation and electron microscopic analyses, and treatments with inhibitors for multivesicular body (MVB) formation revealed that TGase-A is secreted by exosomes, the extracellular vesicles. The 8-residue N-terminal fragment of TGase-A containing the fatty acylation sites was both necessary and sufficient for the exosome-dependent secretion of TGase-A. In conclusion, TG-A is secreted through an unconventional ER/Golgi-independent pathway involving two types of fatty acylations and exosomes.
Primary stimulation of the horseshoe crab innate immune system by lipopolysaccharide (LPS) activates a network of responses to ensure host defense against invading pathogens. Granular hemocytes selectively respond to bacterial lipopolysaccharides (LPS) via a G protein-dependent exocytic pathway that critically depends on the proteolytic activity of the LPS-responsive coagulation factor C. In response to stimulation by LPS, the hemocyte secretes transglutaminase (TG) and several kinds of defense molecules, such as coagulation factors, lectins, antimicrobial peptides, and protein substrates for TG. LPS-induced hemocyte exocytosis is enhanced by a feedback mechanism in which the antimicrobial peptide tachyplesin serves as an endogenous mediator. The coagulation cascade triggered by LPS or β-1,3-D-glucans results in the formation of coagulin fibrils that are subsequently stabilized by TGase-dependent cross-linking. A cuticle-derived chitin-binding protein additionally forms a TGase-stabilized mesh at sites of injury. Invading pathogens are agglutinated by both hemocyte- and plasma-derived lectins. In addition, the proclotting enzyme and tachyplesin functionally convert hemocyanin to phenoloxidase. In the plasma, coagulation factor C acts an LPS-sensitive complement C3 convertase on the surface of Gram-negative bacteria. In this manner, LPS-induced hemocyte exocytosis leads not only to coagulation but also activates a sophisticated innate immune response network that coordinately effects pathogen recognition, prophenoloxidase activation, pathogen clearance, and TG-dependent wound healing. Recently, using molecular biological techniques of Drosophila, we analyze the molecular mechanism of host-commensal microbes cross-talk to maintain a buffered threshold required for immune tolerance against commensal microbes in the gut.Recently, we found that two types of fatty-acid: N-myristoylation and S-palmitoylation modify TG-A. TG-A is one of the two alternative splicing forms of TGs (A and B) and it control not only its localization on the plasma membrane through an unconventional secretory pathway, but also its secretion in response to external stimuli such as bacterial infection. Moreover, ultracentrifugation and electron microscopic analyses, and treatments with inhibitors for multivesicular body (MVB) formation revealed that TGase-A is secreted by exosomes, the extracellular vesicles. The 8-residue N-terminal fragment of TGase-A containing the fatty acylation sites was both necessary and sufficient for the exosome-dependent secretion of TGase-A. In conclusion, TG-A is secreted through an unconventional ER/Golgi-independent pathway involving two types of fatty acylations and exosomes.
Research
Research Interests
Membership in Academic Society
- The molecular mechanism of an unconventional secretion pathway of transglutaminase through lipid modifications inDrosophila
keyword : unconventional secretion pathway, transglutaminase, interacellular protein, lipid modification
2016.04~2018.03. - Molecular mechanism of innate immunity in Drosophila gut
keyword : innate immunity, gut immunity, Drosophila
2006.05~2016.03. - Studies on the molecular mechanism of invertebrate innate immunity
keyword : Innate immunity, Invertebrate, Host defense
1991.04~2010.03.
- Studies on the molecular mechanisms of invertebrates innate immune systems, using horseshoe crabs and Drosophila
Books
1. | T. Shibata and S. Kawabata, Transglutaminases: Multiple functional modifiers and targets for new drug discovery, Springer, 2015.03. |
Reports
Papers
Presentations
- International of Developmental Comparative Immunology
- For exceptional contribution to hte quality of developmental and comparative immunology
Educational
Educational Activities
I am teaching basic biochemistry and protein science for undergraduate students and invertebrate innate immunity for graduate students.
Other Educational Activities
- 2009.04.
- 2008.05.
- 2006.10, The Faculty of Science and Technology at Uppsala University appointed myself as an opponent at the public defense of a Ph.D. student..


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