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Shun-ichiro Kawabata Last modified date：2021.11.02

Professor / Division of Integrative Biology, Laboratory of Protein Sciences
Department of Biology
Faculty of Sciences


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Department of Systems Life Sciences
Graduate School of Systems Life Sciences
Department of Systems Life Sciences
Graduate School of Systems Life Sciences
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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.
Research
Research Interests
  • 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.
Current and Past Project
  • Studies on the molecular mechanisms of invertebrates innate immune systems, using horseshoe crabs and Drosophila
Academic Activities
Books
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1. T. Shibata and S. Kawabata, Transglutaminases: Multiple functional modifiers and targets for new drug discovery, Springer, 2015.03.
Reports
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1. Shibata, T. and Kawabata, S., Pluripotency and a secretion mechanism of Drosophila Transglutaminase., 2018.03.
2. Shun-ichiro Kawabata, Transglutaminase in Invertebrates., In Transglutaminases: multiple functional modifier and targets for new drug discovery (Hitomi, K., Kojima, S., and Fesus, L. Eds.) (2015), pp 117-127, Springer, Tokyo, Heidelberg, New York, and London., 2016.06.
3. Cerenius, L., Kawabata, S., Lee. B. L., Nonaka, M., and Söderhäll, K., Proteolytic cascades and their involvement in invertebrate immunity., Trends in Biochemical Sciences, 2010.07.
4. Kawabata, S., Immunocompetent molecules and their response network in horseshoe crabs. In Invertebrate Immunity , 2010.07.
5. Kawabata, S. and Muta, T., JB Reflections and Perspectives. Sadaaki Iwanaga: discovery of the lipopolysaccharide- and β-1,3-D-glucan-mediated proteolytic cascade and unique proteins in invertebrate immunity., Journal of Biochemistry, 2010.06.
6. Shun-ichiro Kawabata, Takumi Koshiba, Toshio Shibata, The lipopolysaccharide-activated innate immune response network of the horseshoe crab, Invertebrate Survival Journal, 2009.05.
Papers
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1. Yamashita, K., Takeshita, N., Arita, A., Shibata, T., Kobayashi, Y., and Kawabata, S., A mutant equipped with a regenerated disulfide for the missing His loop of a serine protease zymogen in the horseshoe crab coagulation cascade., Journal of Biochemistry, in press, 2021.12, The lipopolysaccharide-triggered coagulation cascade in horseshoe crabs is composed of three zymogens belonging to the trypsinogen family: prochelicerase C, prochelicerase B (proB), and the proclotting enzyme (proCE). Trypsinogen-family members contain three conserved disulfides located around the active site. While it is known that proB evolutionarily lost one of the disulfides, the His-loop disulfide, the roles of the missing His-loop disulfide in proB remain unknown. Here we prepared a proB mutant, named proB-murasame, equipped with a regenerated His-loop disulfide. The activation rate by upstream α-chelicerase C for proB-murasame was indistinguishable from that for wild-type (WT) proB. The resulting protease chelicerase B-murasame exhibited an 8-fold higher kcat value for downstream proCE than WT chelicerase B, whereas the Km value of chelicerase B-murasame was equivalent to that of WT chelicerase B. WT serpins-1, -2, and -3, identified as scavengers for the cascade, had no reactivity against WT chelicerase B, whereas chelicerase B-murasame was inhibited by WT serpin-2, suggesting that WT chelicerae B may trigger as-yet-unsolved phenomena after performing its duty in the cascade. The reconstituted lipopolysaccharide-triggered cascade containing proB-murasame exhibited ~5-fold higher CE production than that containing WT proB. ProB-murasame might be used as a high value-adding reagent for lipopolysaccharide detection..
2. Keisuke Yamashita, Toshio Shibata, Toshiaki Takahashi, Shun-ichiro Kawabata, Roles of the clip domains of two protease zymogens in the coagulation cascade in horseshoe crabs, Journal of Biological Chemistry, 2020.06, The lipopolysaccharide (LPS)-triggered coagulation cascade in horseshoe crabs comprises three protease zymogens, prochelicerase C (proC), prochelicerase B (proB), and the proclotting enzyme (proCE). The presence of LPS results in autocatalytic activation of proC to α-chelicerase C, which, in turn, activates proB to chelicerase B, converting proCE to the clotting enzyme (CE). ProB and proCE contain an N-terminal clip domain, but the roles of these domains in this coagulation cascade remain unknown. Here, using recombinant proteins and kinetics and binding assays, we found that five basic residues in the clip domain of proB are required to maintain its LPS-binding activity and activation by α-chelicerase C. Moreover, an amino acid substitution at a potential hydrophobic cavity in proB’s clip domain (V55A-proB) reduced both its LPS-binding activity and activation rate. WT proCE exhibited no LPS-binding activity, and the WT chelicerase B–mediated activation of a proCE variant with a substitution at a potential hydrophobic cavity (V53A-proCE) was approximately 4-fold slower than that of WT proCE. The kcat/Km value of the interaction of WT chelicerase B with V53A-proCE was 7-fold lower than that of the WT chelicerase B–WT proCE interaction. The enzymatic activities of V55A-chelicerase B and V53A-CE against specific peptide substrates were indistinguishable from those of the corresponding WT proteases. In conclusion, the clip domain of proB recruits it to a reaction center composed of α-chelicerase C and LPS, where α-chelicerase C is ready to activate proB, leading to chelicerase B–mediated activation of proCE via its clip domain..
3. Shibata, T., Kobayashi, Y., Ikeda, Y., and Kawabata, S., Intermolecular autocatalytic activation of serine protease zymogen factor C through an active transition state responding to lipopolysaccharide., Journal of Biological Chemistry, 10.1074/jbc.RA118.002311, 293, 11589-11599, 2018.05, タンパク質組換え体の技術で調製したカブトガニ凝固因子のひとつであるC因子の変異体を用いて、遷移状態のC*因子を捕らえることに成功しました。グラム陰性菌の細胞壁成分であるリポ多糖(LPS)は、過剰に感染すると発熱や多臓器不全、さらには致死性のショック症状を引き起こします。一方で、カブトガニ血球から分泌されるタンパク質分解酵素前駆体のC因子は、ごく微量のLPSに鋭敏に反応して活性型のα-C因子となるため、LPSの高感度検出試薬として利用されてきました。これまで、細菌表面のLPSに結合したC因子は、不安定な中間状態である遷移状態のC*因子となり、C*因子同士が接近して活性型のα-C因子に変換されると推定されていました。この活性化の過程をタンパク質分解酵素前駆体の自己触媒的活性化といいます。しかし、自己触媒的活性化の重要なステージである遷移状態は不安的で寿命が短く、その実態を捕らえることはできませんでした。今回の遷移状態を捕らえる研究手法は、自己触媒的活性化を介して活性化される他のタンパク質分解酵素前駆体の研究に応用されることが期待されます。.
4. Shibata, T., Hadano, J., Kawasaki, D., Dong, X., and Kawabata, S., Drosophila TG-A transglutaminase is secreted via an unconventional Golgi-independent mechanism involving exosomes and two types of fatty acylations, J. Biol. Chem., 2017.05, エクソソーム（exosome）は血液やリンパ液などに含まれる、直径が20nmから100nm程度のナノ小胞です。主に細胞同士のコミュニケーションやがん細胞の浸潤・転移などに関わっており、重要な研究課題です。申請者らの研究グループは、これまでにキイロショウジョウバエ（ハエ）のタンパク質架橋（糊付け）酵素であるトランスグルタミナーゼ（TG）の機能研究を進めてきました。今回、同グループはハエTGの一つであるTG-Aのアミノ末端側に見出された新たな分泌シグナルが脂質修飾を受けて、エクソソームとして分泌されることを明らかにしました。脂質修飾によるタンパク質のエクソソームを介した分泌はこれまでに知られていませんでした。同グループが行ったショウジョウバエを用いた実験においては、エクソソームは細菌や他の細胞に取り込まれ、殺菌や生体の恒常性維持に関わっていることが分かりました。これにより今後はハエの分野に限らず、哺乳類を用いた研究分野全般においてもタンパク質の分泌機構の研究が推進されるきっかけとなることが期待できます。.
5. Maki, K., Shibata, T., and Kawabata, S., Transglutaminase-catalyzed incorporation of polyamines masks the DNA-binding region of the transcription factor relish., J. Biol. Chem., 292, 10723-10734, 2017.04, 免疫系は微生物に対する過剰反応を防ぐために、巧妙な制御機構を備えています。著者らの研究グループは、これまでショウジョウバエを用いて、架橋（糊付け）酵素であるトランスグルタミナーゼ（TG）が、免疫遺伝子のスイッチを入れるNF-κBと呼ばれるタンパク質（転写因子）のひとつであるレリッシュの分子の間を架橋することを報告していました。今回、細胞の核内において、トランスグルタミナーゼ（TG）の架橋反応を介して、レリッシュ分子内の特定のアミノ酸（グルタミン）にポリアミンが架橋されることで、レリッシュのDNA結合能力が阻害され、過剰な免疫遺伝子の発現が抑制されることが判明しました。哺乳類においては、NF-κBの過剰な活性化は炎症疾患の原因となります。また哺乳類と昆虫においては、免疫の情報伝達経路のひとつであるNF-κB経路は相互に類似しており、進化的に保存されています。今回の発見により炎症疾患の原因解明や治療に寄与すると期待されます。.
6. Mizumura, H., Ogura, N., Aketagawa, J., Aizawa, M., Kobayashi, Y., Kawabata, S., and Oda, T., Genetic engineering approach to develop next-generation reagents for endotoxin quantification., Innate Immunity, DOI: 10.1177/1753425916681074, 23, 136-146, 2017.03, カブトガニの体液凝固因子群の組換えタンパク質を調製して、グラム陰性菌の細胞壁成分のリポ多糖（ＬＰＳ）を検出する方法を開発した。これまで、生きたカブトガニから血球細胞を回収して、体液凝固成分を抽出し、リムスル試薬として調製する必要があったが、今回の組換えタンパク質の調製法の確立により、将来的にも安定的にＬＰＳ検出試薬の提供が可能となった。.
7. Sekihara, S., Shibata, T., Hyakkendani, M., and Kawabata, S., RNA interference directed against the transglutaminase gene triggers dysbiosis of gut microbiota in Drosophila. , J. Biol. Chem., doi:10.1074/jbc.M116.761791, 291, 25077-25087, 2016.11, 宿主の腸管は常に多種多様な感染微生物にさらされおり、宿主は巧妙に制御された免疫機構を発達させることで、腸内細菌叢の恒常性を保っています。著者らは、次世代シークエンサーによりショウジョウバエの腸内細菌の遺伝子解析を行い、野生型とトランスグルタミナーゼ遺伝子をノックダウンしたハエでは腸内細菌叢が大きく異なっていることを見出しました。また、腸管から単離した4種の細菌株（SK1～SK4）の抗菌ペプチドと活性酸素に対する耐性を比較したところ、常在菌が腸管内の環境に順応すると、試験管での培養した際の菌とは異なる性質を示すことが推定されました。さらに、無菌バエにSK1とSK4を1：1の比率で感染させると菌を単独で感染させたハエよりも短命になることが判明しました。今回の研究により、単離した細菌を無菌ハエに摂食させることで、腸内環境における細菌間、あるいは細菌と宿主間の相互作用研究に利用できることが判明しました。ハエだけでなく、ほ乳類やヒトに共生している腸内細菌叢の研究にも応用できる実験系であり、今後、宿主・細菌の共生の分子機構の理解に寄与することが期待されます。.
8. Shun-ichiro Kawabata, Crosslinking of a peritrophic matrix protein protects gut epithelia from bacterial exotoxins., PLoS Pathog., 10.1371/journal.ppat.1005244, 11, e1005244, 2015.10, Transglutaminase (TG) catalyzes protein-protein crosslinking, which has important and diverse roles in vertebrates and invertebrates. Here we demonstrate that Drosophila TG crosslinks drosocrystallin, a peritrophic matrix protein, to form a stable fiber structure on the gut peritrophic matrix. RNA interference (RNAi) of the TG gene was highly lethal in flies and induced apoptosis of gut epithelial cells after oral infection with Pseudomonas entomophila. Moreover, AprA, a metalloprotease secreted by P. entomophila, digested non-crosslinked drosocrystallin fibers, but not drosocrystallin fibers crosslinked by TG. In vitro experiments using recombinant drosocrystallin and monalysin proteins demonstrated that monalysin, a pore-forming exotoxin of P. entomophila, was adsorbed on the crosslinked drosocrystallin fibers in the presence of P. entomophila culture supernatant. In addition, gut-specific TG-RNAi flies had a shorter lifespan than control flies after ingesting P. entomophila, whereas the lifespan after ingesting AprA-knockout P. entomophila was at control levels. We conclude that drosocrystallin fibers crosslinked by TG, but not non-crosslinked drosocrystallin fibers, form an important physical barrier against exotoxins of invading pathogenic microbes..
9. Shun-ichiro Kawabata, Crosslinking of a peritrophic matrix protein protects gut epithelia from bacterial exotoxins., PLoS Pathog., 10.1371/journal.ppat.1005244, 11, e1005244, 2015.10, Transglutaminase (TG) catalyzes protein-protein crosslinking, which has important and diverse roles in vertebrates and invertebrates. Here we demonstrate that Drosophila TG crosslinks drosocrystallin, a peritrophic matrix protein, to form a stable fiber structure on the gut peritrophic matrix. RNA interference (RNAi) of the TG gene was highly lethal in flies and induced apoptosis of gut epithelial cells after oral infection with Pseudomonas entomophila. Moreover, AprA, a metalloprotease secreted by P. entomophila, digested non-crosslinked drosocrystallin fibers, but not drosocrystallin fibers crosslinked by TG. In vitro experiments using recombinant drosocrystallin and monalysin proteins demonstrated that monalysin, a pore-forming exotoxin of P. entomophila, was adsorbed on the crosslinked drosocrystallin fibers in the presence of P. entomophila culture supernatant. In addition, gut-specific TG-RNAi flies had a shorter lifespan than control flies after ingesting P. entomophila, whereas the lifespan after ingesting AprA-knockout P. entomophila was at control levels. We conclude that drosocrystallin fibers crosslinked by TG, but not non-crosslinked drosocrystallin fibers, form an important physical barrier against exotoxins of invading pathogenic microbes..
10. Shun-ichiro Kawabata, Factor B is the second lipopolysaccharide-binding protease zymogen in the horseshoe crab coagulation cascade., J. Biol. Chem. , doi:10.1074/jbc.M115.653196, 290, 19379-19386, 2015.07.
11. Shun-ichiro Kawabata, The N-terminal Arg residue is essential for autocatalytic activation of a lipopolysaccharide-responsive protease zymogen, Journal of Biological Chemistry , 10.1074/jbc.M114.586933, 289, 25987-25995, 2014.07, Factor C, a serine protease zymogen involved in innate immune responses in horseshoe crabs, is known to be autocatalytically activated on the surface of bacterial lipopolysaccharides, but the molecular mechanism of this activation remains unknown. In this study, we show that wild-type factor C expressed in HEK293S cells exhibits a lipopolysaccharide-induced activity equivalent to that of native factor C. Analysis of the N-terminal addition, deletion, or substitution mutants shows that the N-terminal Arg residue and the distance between the N-terminus and the tripartite of lipopolysaccharide-binding site are essential factors for the autocatalytic activation, and that the positive charge of the N-terminus may interact with an acidic amino acid(s) of the molecule to convert the zymogen into an active form. Chemical cross-linking experiments indicate that the N-terminus is required to form a complex of the factor C molecules in sufficiently close vicinity to be chemically cross-linked on the surface of lipopolysaccharides. We propose a molecular mechanism of the autocatalytic activation of the protease zymogen on lipopolysaccharides functioning as a platform to induce specific protein-protein interaction between the factor C molecules..
12. Shun-ichiro Kawabata, Transglutaminase-Catalyzed Protein-Protein Cross-Linking Suppresses the Activity of the NF-κB-like Transcription Factor Relish, Science Signaling, DOI: 10.1126/scisignal.2003970, 6, 285, ra61, 2013.07, Cross-linking of proteins by mammalian transglutaminases (TGs) plays important roles in physiological
phenomena such as blood coagulation and skin formation. We show that Drosophila TG suppressed innate
immune signaling in the gut. RNA interference (RNAi) directed against TG reduced the life span of
flies reared under conventional nonsterile conditions but not of those raised under germ-free conditions. In
conventionally reared flies, TG RNAi enhanced the expression of genes encoding antimicrobial peptides in the
immune deficiency (IMD) pathway. Wild-type flies that ingested gut lysates prepared from conventionally
reared TG RNAi–treated flies had shorter life spans. In conventionally reared flies, TG RNAi triggered
apoptosis in the gut and induced the nuclear translocation of Relish, the NF-kB (nuclear factor kB)–like
transcription factor of the IMD pathway. Wild-type flies that ingested synthetic amine donors, which inhibit
the TG-catalyzed protein-protein cross-linking reaction, showed nuclear translocation of Relish and enhanced
expression of genes encoding IMD-controlled antimicrobial peptide genes in the gut. We conclude
that TG-catalyzed Relish cross-linking suppressed the IMD signaling pathway to enable immune tolerance
against commensal microbes..
13. Tagawa, K., Yoshihara, Y., Shibata, T., Kitazaki, K., Endo, Y., Fujita, T., Koshiba, T., and Kawabata, S., Microbe-specific C3b deposition in the horseshoe crab complement system in a C2/factor B-dependent or -independent manner., PLoS ONE, doi:10.1371/journal.pone.0036783, 7, e36783, 2012.05.
14. Koshiba, T., Yasukawa, K., Yanagi, Y., and Kawabata, S., Mitochondrial membrane potential is involved in the MAVS-mediated antiviral signaling., Science Signaling, 4, ra7 , 2011.02, Mitochondria, dynamic organelles that undergo cycles of fusion and fission, are the powerhouses of eukaryotic cells and are also involved in cellular innate antiviral immunity in mammals. Mitochondrial antiviral immunity depends on activation of the cytoplasmic retinoic acid–inducible gene I (RIG-I)–like receptor (RLR) signaling pathway and the participation of a mitochondrial outer membrane adaptor protein called MAVS (mitochondrial antiviral signaling). We found that cells that lack the ability to undergo mitochondrial fusion as a result of targeted deletion of both mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2) exhibited impaired induction of interferons and proinflammatory cytokines in response to viral infection, resulting in increased viral replication. In contrast, cells with null mutations in either Mfn1 or Mfn2 retained their RLR-induced antiviral responses. We also found that a reduced mitochondrial membrane potential (DYm) correlated with the reduced antiviral response. The dissipation in DYm did not affect the activation of the transcription factor interferon regulatory factor 3 downstream of MAVS, which suggests that DYm and MAVS are coupled at the same stage in the RLR signaling pathway. Our results provide evidence that the physiological function of mitochondria plays a key role in innate antiviral immunity..
15. Koshiba, T., Holman, H. A., Kubara, K., Yasukawa, K., Kawabata, S., Okamoto, K., Macfarlane, and Shaw, J. M., Structure-function analysis of the yeast Miro GTPase, Gem1p: implications for mitochondrial inheritance., J. Biol. Chem. , 10.1074/jbc.M110.180034, 286, 354-362, 2011.01.
16. Haipeng, L., Wu, C., Matsuda, Y., Kawabata, S., Lee, B. L., Söderhäll, K., and Söderhäll, I., Peptidoglycan activation of the proPO-system without a peptidoglycan receptor protein (PGRP)? , Dev. Comp. Immunol., 35, 51-61, 2011.01.
17. Shibata, T., Ariki, S., Shinzawa, N., Miyaji, R., Suyama, H., Sako, M., Inomata, N., Koshiba, T., Kanuka, H., and Kawabata, S., Protein Crosslinking by Transglutaminase Controls Cuticle Morphogenesis in Drosophila., PLoS ONE, 10.1371/journal.pone.0013477, 5, e13477, 2010.10.
18. Yasukawa, K., Oshiumi, H., Takeda, M., Ishihara, N., Yanagai, Y., Seya, T., Kawabata, S., and Koshiba, T, Mitofusin 2 inhibits mitochondorial antiviral signaling, Science Signaling , 2, ra47 , 2009.08.
19. S. Ariki, S. Takahara, T. Shibata, T. Fukuoka, A. Ozaki, Y. Endo, T. Fujita, T. Koshiba, and S. Kawabata, Factor C acts as a lipopolysaccharide-responsive C3 convertase in horseshoe crab complement activation, Journal of Immunology, 181巻、7994-8001, 2008.12.
20. Matusda, Y., Koshiba,T., Osaki, T., Suyama, H., Arisaka, F., Toh, Y., and Kawabata, S., An arthropod cuticular chitin-binding protein endows injured sites with transglutaminase-dependent mesh. , Journal of Biological Chemistry, 282巻、37316-37324 , 2007.12.
21. Matsuda, Y., Osaki, T., Hashii, T., Koshiba, T., and Kawabata, S., A cysteine-rich protein from an arthropod stabilizes clotting mesh and immobilizes bacteria at injured sites., Journal of Biological Chemistry, 282巻, 37316-37324 , 2007.11.
22. Takumi Koshiba, Tomoyuki Hashii, Shun-ichiro Kawabata, A structural perspective on the interaction between lipopolysaccharide and factor C, a receptor involved in recognition of Gram-negative bacteria., Journal of Biological Chemistry, 282巻3962-3967, 2007.02.
23. Manabu Iijima, Tomonori Hashimoto, Yasuyuki Matsuda, Taku Nagai, Youichiro Yamano, Tomohiko Ichi, Tsukasa Osaki, Shun-ichiro Kawabata, Comprehensive sequence analysis of horseshoe crab cuticular proteins and their involvement in transglutaminase-dependent cross-linking, FEBS Journal, 10.1111/j.1742-4658.2005.04891.x, 272, 18, 4774-4786, 2005.08.
24. Aya Osaki, Shigeru Ariki, Shun-ichiro Kawabata, An antimicrobial peptide tachyplesin acts as a secondary secretagogue and amplifies lipopolysaccharide-induced hemocyte exocytosis, FEBS Jounarl, 10.1111/j.1742-4658.2005.04800.x, 272, 15, 3863-3871, 272, 3863-3871, 2005.06.
25. Ariki, S., Koori, K., Osaki, T., Motoyama, K., Inamori, K., and Kawabata, S, A serine protease zymogen functions as a pattern-recognition receptor for lipopolysaccharides., Proc. Natl. Acad. Sci. USA, 101, 953-958, 2004.01.
Presentations
 Show All Presentations >>
1. Shun-ichiro Kawabata , Drosophila transglutaminase (dTG) regulates transcriptional activity by incorporating polyamines into the NF-kB-like transcription factor Relish
, 2018.06.
2. Shibata, T., Maki, K., Fujikawa, T., and Kawabata, S., Transglutaminase-catalyzed crosslinking of peritrophic matrix proteins maintains the gut epithelial immunity in Drosophila. , Entomology 2017 in the Annual meeting of Entomological Society of America., 2017.11.
3. hibata, T., Maki, K., Fujikawa, T., and Kawabata, S., Transglutaminase-catalyzed crosslinking of peritrophic matrix proteins maintains the gut epithelial immunity in Drosophila., European Drosophila Research Conference, 2017.09.
4. Shun-ichiro Kawabata, Transglutaminase-catalyzed relish crosslinking suppresses innate immune signaling in the Drosophila., Gordon Research Conference on Transglutaminase in Human Disease Processes, 2014.06.
5. Shun-ichiro Kawabata, Transglutaminase-Catalyzed Protein-Protein Crosslinking Maintains the Gut Epithelial Immunity in Drosophila., The 55th Annual Drosophila Research Conference, 2014.03.
6. Shun-ichiro Kawabata, Transglutaminase-catalyzed crosslinking suppresses the activity of the NF-κB-like transcription factor relish in Drosophila., The First Asian Invertebrate Immunology Symposium, 2014.02.
7. Shun-ichiro Kawabata, Transglutaminase-catalyzed protein crosslinking suppresses innate immune signaling in the Drosophila gut, 国際エンドトキシン自然免疫学会, 2012.09, Mammalian transglutaminases (TGs) play important roles in numerous physiological phenomena such as blood coagulation and skin formation via protein-protein crosslinking. Recently, we reported that the RNAi of the TG gene in Drosophila causes a pupal semi-lethal phenotype and abnormal morphology, including abnormal wing formation and abdominal melanization (PLoS ONE, 2010). TG-RNAi flies had a shorter life span than their wild-type counterparts, and approximately 90% of flies died within 30 days after eclosion under conventionally reared conditions. We show that Drosophila cytoplasmic TG suppresses innate immune signaling in the gut. TG-RNA-mediated interference (TG-RNAi) caused a short life span under non-sterile conventionally reared conditions, but not under germ-free conditions. Under conventionally reared conditions, TG-RNAi enhanced the expression of immune deficiency (IMD) pathway-controlled antimicrobial peptide genes. Ingestion of gut lysates prepared from conventionally reared TG-RNAi flies into non-TG-RNAi flies resulted in the short life span of the recipients. TG-RNAi under conventionally reared conditions triggered severe apoptosis in the gut and induced the translocation of Relish, the NF-κB-like transcription factor of the IMD pathway, from the cytoplasm to the nucleus. Ingestion of synthetic amine donors by non-TG-RNAi flies, which inhibits the TG-catalyzed protein-protein crosslinking reaction, also induced the nuclear translocation of Relish and enhanced the expression of IMD-controlled antimicrobial peptide genes in the gut. We conclude that TG-catalyzed Relish crosslinking suppresses the IMD-signaling pathway to maintain a buffered threshold required for immune tolerance against commensal microbes..
8. Horseshoe crab factor G utilizes a carbohydrate-binding cleft that is conserved among invertebrates and bacteria for the recognition of β-1,3-glucans. .
9. A structural perspective on the interaction between lipopolysaccharide and horseshoe crab factor C.
10. Amplification of the horseshoe crab innate immune reaction by an antimicrobial peptide.
Membership in Academic Society
  • International of Developmental Comparative Immunology
Awards
  • 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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