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The elucidation of the mechanism suppressing the degradation of claudin proteins by the TACSTD2 protein

Research Project

Project/Area Number 24791868
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

NAKATSUKASA Mina  京都府立医科大学, 医学部附属病院, 専攻医 (70614022)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords膠様滴状角膜ジストロフィ / TACSTD2 / タイトジャンクション / CLDN1 / CLDN7
Research Abstract

The TACSTD2 protein identified as a causative gene for Gelatinous Drop-Like Corneal Dystrophy (GDLD) was directly bound to CLDN1 and CLDN7 proteins, and we found that extracellular region of the TACSTD2 protein is essential for its binding to the CLDN7 protein. We also found that AxxxG motif in the transmembrane domain is important for the binding of the TACSTD2 protein to the CLDN7 protein. Although the TJP1 protein expression level was found to be somewhat more reduced in the GDLD cornea than in the normal human cornea, the TJP1 protein was observed at the apical surface of cornea epithelium. Moreover, in the immortalized corneal epithelial cells and conjunctival epithelial cells derived from the GDLD patient, the TJP1 and the occludin proteins were observed to be localized at the cell-to-cell borders, and the epithelial barrier function was found to be low.
The findings of this study indicate that in GDLD corneal epithelial cells, the tight junction is formed on the low level.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2014 2013 2012 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (16 results)

  • [Journal Article] Establishment of a human corneal epithelial cell line lacking the functional TACSTD2 gene as an in vitro model for gelatinous drop-like dystrophy.2013

    • Author(s)
      Kitazawa K, Kawasaki S, Shinomiya K, Aoi K, Matsuda A, Funaki T, Yamasaki K, Nakatsukasa M, Ebihara N, Murakami A, Hamuro J, Kinoshita S.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 8 Issue: 8 Pages: 5701-11

    • DOI

      10.1167/iovs.12-11043

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Investigation of protein kinase C alpha in corneal epithelial cells derived from a gelatinous drop-like corneal dystrophy patient2014

    • Author(s)
      Kitazawa K, Kawasaki S, Ueno M, Tanaka H, Shinomiya K, Nakatsukasa M, Kinoshita S
    • Organizer
      ARVO
    • Place of Presentation
      Orlando USA
    • Year and Date
      2014-05-08
    • Related Report
      2013 Final Research Report
  • [Presentation] Theoretical assessment for the gene therapy of gelatinous drop-like corneal dystrophy2014

    • Author(s)
      Kawasaki S, Kitazawa K, Shinomiya K, Nakatsukasa M, Tsujikawa M, Matsuda A, Murakami A, Nishida K, Kinoshita S
    • Organizer
      ARVO
    • Place of Presentation
      Orlando USA
    • Year and Date
      2014-05-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 膠様滴状角膜ジストロフィにおけるタイトジャンクション構成機構2014

    • Author(s)
      中司美奈, 川崎諭, 北澤耕司, 篠宮克彦, 木下茂
    • Organizer
      第38回日本角膜学会総会
    • Place of Presentation
      沖縄 日本
    • Year and Date
      2014-01-30
    • Related Report
      2013 Final Research Report
  • [Presentation] GDLD 患者由来の不死化角膜上皮細胞における PKC-α発現の検討2014

    • Author(s)
      北澤耕司, 川崎諭, 上野盛夫, 田中寛, 篠宮克彦, 中司美奈, 木下茂
    • Organizer
      第118回日本眼科学会総会
    • Place of Presentation
      東京 日本
    • Related Report
      2013 Final Research Report
  • [Presentation] 膠様滴状角膜ジストロフィにおけるタイトジャンクション構成機構2014

    • Author(s)
      中司美奈、川崎諭、北澤耕司、篠宮克彦、木下茂
    • Organizer
      第38回日本角膜学会総会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Annual Research Report
  • [Presentation] GDLD患者由来の不死化角膜上皮細胞におけるPKC-α発現の検討2014

    • Author(s)
      北澤耕司、川崎諭、上野盛夫、田中寛、篠宮克彦、中司美奈、木下茂
    • Organizer
      第118回日本眼科学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Theoretical assessment for the gene therapy of gelatinous drop-like corneal dystrophy2014

    • Author(s)
      川崎諭、北澤耕司、篠宮克彦、中司美奈、辻川元一、松田彰、村上晶、西田幸二、木下茂
    • Organizer
      The Association for Research in Vision and Ophthalmology 2014
    • Place of Presentation
      アメリカ、オーランド
    • Related Report
      2013 Annual Research Report
  • [Presentation] Investigation of protein kinase C alpha in corneal epithelial cells derived from a gelatinous drop-like corneal dystrophy patient2014

    • Author(s)
      北澤耕司、川崎諭、上野盛夫、田中寛、篠宮克彦、中司美奈、木下茂
    • Organizer
      The Association for Research in Vision and Ophthalmology 2014
    • Place of Presentation
      アメリカ、オーランド
    • Related Report
      2013 Annual Research Report
  • [Presentation] TACSTD2 遺伝子による角膜上皮タイトジャンクション機能抑制機構の解明2013

    • Author(s)
      中司美奈
    • Organizer
      第37回日本角膜学会総会
    • Place of Presentation
      和歌山 日本
    • Year and Date
      2013-02-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Investigation of gene therapy using immortalized cells derived from a gelatinous drop-like corneal dystrophy patient2013

    • Author(s)
      Kitazawa K, Kawasaki S, Aoi K, Shinomiya K, Matsuda A, Hunaki T, Nakatsukasa M, Hamuro J, Murakami A, Kinoshita S
    • Organizer
      ARVO
    • Place of Presentation
      Seattle USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Investigation of Gene Therapy Using Immortalized Cells Derived from a Gelatinous Drop-Like Corneal Dystrophy Patient2013

    • Author(s)
      北澤耕司、川崎諭、青井啓太、篠宮克彦、松田彰、舟木俊成、中司美奈、羽室淳爾、村上晶、木下茂
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      アメリカ、シアトル
    • Related Report
      2013 Annual Research Report
  • [Presentation] Establishiment of immortalized corneal and conjunctival epithelial cells lacking the functional TACSTD2 gene2012

    • Author(s)
      Kitazawa K, Kawasaki S, Shinomiya K, Matsuda A, Hunaki T, Nakatsukasa M, Yamasaki K, Ebihara N, Murakami A, Kinoshita S
    • Organizer
      ARVO
    • Place of Presentation
      Florida USA
    • Year and Date
      2012-05-07
    • Related Report
      2013 Final Research Report
  • [Presentation] 膠様滴状角膜ジストロフィ患者由来の不死化角膜および結膜上皮細胞の 樹 立2012

    • Author(s)
      北澤耕司, 川崎諭, 篠宮克彦, 松田彰, 舟木俊成, 山崎健太, 中司美奈, 海老原伸行, 村上晶, 木下茂
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京 日本
    • Year and Date
      2012-04-05
    • Related Report
      2013 Final Research Report
  • [Presentation] TACSTD2遺伝子による角膜上皮タイトジャンクション機能制御機構の解明

    • Author(s)
      中司 美奈
    • Organizer
      第37回日本角膜学会総会
    • Place of Presentation
      和歌山
    • Related Report
      2012 Research-status Report
  • [Presentation] 膠様滴状角膜ジストロフィ患者由来の不死化角膜および結膜上皮細胞の樹立

    • Author(s)
      1. 北澤耕治,川崎諭,篠宮克彦,松田彰,舟木俊成,山崎健太,中司美奈,海老原伸行,村上晶,木下 茂
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Establishment Of Immortalized Corneal And Conjunctival Epithelial Cells Lacking The Functional Tacstd2 Gene

    • Author(s)
      北澤耕治,川崎諭,篠宮克彦,松田彰,舟木俊成,中司美奈,山崎健太,海老原伸行,村上晶,木下茂
    • Organizer
      The Association for Research in Vision and Ophthalmology2012
    • Place of Presentation
      アメリカ、フォートローダーデール
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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