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Research on the mechanism of tight jundan regulafion by using botulinum toxir complex

Research Project

Project/Area Number 18570178
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionOsaka University

Principal Investigator

FUJINAGA Yukako  Osaka University, Research Institute for Microbial Diseases, SA, Associate Professor (60252954)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordstight junction / epithelial cell / cell to cell function / glycoprotein / botulinum toxin / 膜タンパク質
Research Abstract

The type B botulinum neurotoxin (BoNT) elicits flaccid paralysis and death in humans by intoxicating peripheral nerves after oral absorption. Here, we examine the function of the hemagglutinin (HA), a non-toxic component of the large 16S BoNT complex. We find that the HA acts in the intestine to disrupt epithelial barrier function by opening intercellular tight and adherens junctions. This allows transport of BoNT and other large solutes into the systemic circulation and explains how the type B BoNT complexes are efficiently absorbed. In vitro, HA appears to act on the epithelial cell via the basolateral membrane only, suggesting the possibility of another step in the absorptive process. These studies show that the 16S BoNT complex is a multi-functional protein assembly equipped with the machinery to efficiently breach the intestinal barrier and act systemically on peripheral nerves.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (32 results)

All 2008 2007 2006

All Journal Article (13 results) (of which Peer Reviewed: 3 results) Presentation (18 results) Book (1 results)

  • [Journal Article] The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption.2008

    • Author(s)
      T. Matsumura, et. al.
    • Journal Title

      Cellular Microbiology 10

      Pages: 355-364

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption2008

    • Author(s)
      Matsumura, T., et. al.
    • Journal Title

      Cellular Microbiology 10

      Pages: 355-364

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption.2008

    • Author(s)
      T. Matsumura, Y. Jin, et. al.
    • Journal Title

      Cellular Microbiology 10

      Pages: 355-364

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human milk SIgA binds to botulinum type B 16S toxin and limits toxin adherence on T84 cells.2007

    • Author(s)
      T. Matsumura, et. al.
    • Journal Title

      Biochemical and Biophysical Research Communications 352

      Pages: 867-872

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Human milk S1gAbinds to botulinum type B 165 toxin and limits toxin adherence on T84 cells2007

    • Author(s)
      Matsumura, T., et. al.
    • Journal Title

      BBRC 352

      Pages: 867-872

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Humanmilk STgA binds to botulinum type B 16S toxin and Timits toxin adherence on T84 cells.2007

    • Author(s)
      T. Matsumura, Y. Fujinaga, Et. al.
    • Journal Title

      Biochemical and Biophysical Research Communications 352

      Pages: 867-872

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Interactions of botulinum progenitor toxin and cholera toxin with host intestinal epithelial cells.2006

    • Author(s)
      Y. Fujinaga
    • Journal Title

      J. Toxicol. Toxin Rev. 25

      Pages: 47-59

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Transport of bacterial toxins into target cells: Pathways followed by cholera toxin and botulinum progenitor toxin.2006

    • Author(s)
      Y. Fujinaga
    • Journal Title

      J. Biochem(Tokyo) 140

      Pages: 155-160

    • NAID

      10018842667

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 細菌毒素の細胞内輸送機構〜みえてきた細菌毒素が持つ巧妙な戦略〜2006

    • Author(s)
      藤永由佳子
    • Journal Title

      化学療法の領域 22.2

      Pages: 231-237

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Interactions of botulinum progenitor toxin and cholera toxin with host intestinal epithelial cells2006

    • Author(s)
      Fujinaga, Y
    • Journal Title

      J. Toxicol.Toxin Rev 25

      Pages: 47-59

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Fujinaga. Transport of bacterial toxins into target cells : Pathways followed by cholera toxin and botulinum progenitor toxin2006

    • Author(s)
      Y., Fujinaga
    • Journal Title

      J.Biochem (Tokyo) 140

      Pages: 155-160

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Interactions of botulinum progenitor toxin and cholera toxin with host intestinal epithelial cells.2006

    • Author(s)
      Y-Fujinaga
    • Journal Title

      J. Toxicol. Toxin Rev. 25

      Pages: 47-59

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Transport og\f bacterialtoxins into target cells: Pathways followed by cholera toxin and botulinum progenitor toxin.2006

    • Author(s)
      Y-Fujinaga
    • Journal Title

      J. Biochem (Tokyo) 140

      Pages: 155-160

    • Related Report
      2006 Annual Research Report
  • [Presentation] ボツリヌスHA複合体構成サブユニットの有する腸管上皮細胞間バリア破壊活性の解析2008

    • Author(s)
      竹ケ原夕紀、金 英姫、菅原庸、松村拓大、藤永由佳子
    • Organizer
      第81回日本細菌学会総会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A new function of botulinum toxin associated proteins: The HA component disrupts intestinal epithelial intercellular junctions to increase toxin absorption.2007

    • Author(s)
      Y. Fujinaga
    • Organizer
      2007 International RIMD-CVRDC Joint Symposium
    • Place of Presentation
      Suita, Osaka, Japan
    • Year and Date
      2007-12-18
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] A new function of botulinum toxin associated proteins : The HA component disrupts intestinal epithelial intercellular junctions to increase toxin absorption2007

    • Author(s)
      Fujinaga, Y
    • Organizer
      International RIMD-CVRDC Joint Symposium Suita
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2007-12-18
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ボツリヌスHA複合体による腸管上皮細胞間バリア破壊機構の解析2007

    • Author(s)
      竹ケ原夕紀、金 英姫、松村拓大、菅原 庸、藤永由佳子
    • Organizer
      第60回日本細菌学会関西支部会
    • Place of Presentation
      大阪
    • Year and Date
      2007-11-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Mechanism of intestinal absorption of botulinum toxin.2007

    • Author(s)
      Y. Fujinaga
    • Organizer
      The 2nd Thailand-Japan Joint Forum on Infectious Diseases,
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2007-10-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanism of intestinal absorption of botulinum toxin2007

    • Author(s)
      Fujinaga, Y
    • Organizer
      The 2nd Thailand-Japan Joint Forum on Infectious Diseases (Invited speaker)
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2007-10-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanism of intestinal absorption of botulinum toxin.2007

    • Author(s)
      Y.fujinaga
    • Organizer
      The 2nd Thailand-Japan Joint Forum on In fectious Diseases,
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2007-10-08
    • Related Report
      2007 Annual Research Report
  • [Presentation] ボツリヌス神経毒素複合体の腸管上皮細胞バリア通過機構2007

    • Author(s)
      藤永由佳子、松村拓大、金 英姫、竹ケ原夕紀、株本祐子、小熊惠二
    • Organizer
      感染マトリックス 応用ゲノム ジョイントミーティング 第1回細菌学・若手コロッセウム
    • Place of Presentation
      神戸
    • Year and Date
      2007-01-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Transepithelial transport of the botulinum toxin via trans cellular and paracellular routes2007

    • Author(s)
      Y. Fujinaga, et. al.
    • Organizer
      International Symposium "Membrane traffic"
    • Place of Presentation
      Awaji-shima Hyogo, Japan.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Disruption of the intestinal paracellular barrier by botulinum toxin complex.2007

    • Author(s)
      T. Matsumura, Y. Jin, Y. Kabumoto, Y. Takegahara, Y Sugawara, K. Oguma, W. I. Lencer, and Y. Fujinaga
    • Organizer
      The 7th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Hyogo, Japan
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] ボツリヌス神経毒素複合体に含まれる無毒成分(HA)は腸管上皮細胞バリア機能を破壊する2007

    • Author(s)
      松村拓大、金 英姫、株本祐子、竹ケ原夕紀、菅原 庸、小熊惠二、藤永由佳子
    • Organizer
      第30回日本分子生物学会年回・第80回日本生化学会大会 合同大会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] ボツリヌス神経毒素複合体の腸管上皮バリア通過機構2007

    • Author(s)
      松村拓大、金 英姫、株本祐子、竹ケ原夕紀、菅原 庸、小熊惠二、藤永由佳子
    • Organizer
      第54回毒素シンポジウム
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] ボツリヌス神経毒素複合体の腸管からの吸収機構について2007

    • Author(s)
      藤永由佳子、松村拓大、金 英姫、竹ケ原夕紀、株本祐子、小熊惠二
    • Organizer
      第80回日本細菌学会総会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ボツリヌス神経毒素複合体の腸管上皮細胞バリア通過機構について2007

    • Author(s)
      松村 拓大、金 英姫、竹ケ原 夕紀、株本 祐子、小熊 惠二、藤永 由佳子
    • Organizer
      文部科学省特定領域研究 感染マトリックス 第5回感染症沖縄フォーラム
    • Place of Presentation
      沖縄
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Lencer WI, and Fujinaga Y, The HA proteins of botulinum toxin induce paracellular leakage in intestinal epithelial cells to increase toxin absorption2007

    • Author(s)
      Matsumura, T., Jin, Y., Kabumoto, Y., Takegahara, Y., Oguma, K
    • Organizer
      ETOX 13 European Workshop on Bacterial Protein Toxins
    • Place of Presentation
      San Martino al Cimino, Italy
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Disruption of the intestinal paracellular barrier by botulinum toxin complex2007

    • Author(s)
      Matsumura, T., Jin, Y., Kabumoto, Y., Takegahara, Y., Sugawara, Y., Oguma, K., Lencer, WI., Fujinaga, Y
    • Organizer
      The 7th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Hyogo, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Transepithelial transport of the botulinum toxin via trans cellular and paracellular routes2007

    • Author(s)
      Fujinaga, Y., Matsumura, T., Jin, Y., Takegahara, Y., Sugawara, Y
    • Organizer
      IntemationalSymposium "Membranetraffic"Awaji-shima
    • Place of Presentation
      Hyogo,Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ボツリヌス神経毒素複合体の腸管上皮細胞バリア通過機構の解析2006

    • Author(s)
      藤永由佳子、松村拓大、金 英姫、竹ケ原夕紀、株本祐子
    • Organizer
      文部科学省特定領域研究 メンブレントラフィック〜分子機構から高次機能への展開〜 第4回班会議
    • Place of Presentation
      香川県小豆島
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 第29回阿蘇シンポジウム記録 感染防御のBird's-eye view[ボツリヌス毒素複合体と宿主腸管上皮細胞]2006

    • Author(s)
      藤永由佳子
    • Publisher
      南山堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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