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Molecular regulation of cell adhesion machinery by epidermolysis bullosa-associated protein Exophilin-5

Research Project

Project/Area Number 21K06866
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionGunma University

Principal Investigator

Matsunaga Kohichi  群馬大学, 生体調節研究所, 助教 (20570162)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords表皮水疱症 / Exophilin-5 / Rab27 / 調節性分泌 / 細胞接着 / Exophilin / 皮膚細胞
Outline of Research at the Start

表皮水疱症は、先天的に皮膚が脆弱で、わずかな外力で全身に水疱、びらんの形成が起こる遺伝性疾患である。最近Exophilin-5遺伝子の異常が単純型表皮水疱症を引き起こすことが報告された。Exophilin-5は調節性分泌を制御する、単量体GTPase Rab27のエフェクターであるが、機能解析が進んでいない。本研究は、なぜExophilin-5の欠損が単純型表皮水疱症を引き起こすのか、表皮細胞でのExophilin-5の役割を解明し、その破綻によって起こる表皮水疱症の病態生理を明らかにする。

Outline of Final Research Achievements

To investigate the role of Exophilin-5 in epidermal cells and its molecular mechanism, we have searched for specific binding proteins of Exophilin-5 and several proteins involved in cell adhesion were identified. Analysis of these novel binding proteins revealed that Exophilin-5 functions not only in hemi-desmosome formation but also in the formation of other adhesion machinery. Furthermore, deletion of Exophilin-5 inhibited hemi-desmosome and other adhesion machinery formation and reduced cell adhesion ability. We examined wound healing assay in knockout mouse skin and the wound healing of knockout mice was delayed compared with wild-type mice.
These results indicate that Exophilin-5 plays an important role in the homeostasis of the cell adhesion machinery.

Academic Significance and Societal Importance of the Research Achievements

表皮水疱症は、重篤な先天性疾患であり、日常生活が著しく制限され、未だに対症療法しかない難病である。Exophilin-5は単純型表皮水疱症の原因遺伝子として同定されたが、その詳細な作用機序はほとんどわかっていなかった。本研究により、Exophilin-5が複数の細胞接着装置構成たんぱく質と相互作用し、細胞接着装置の恒常性維持において重要な役割を持っていることが示されたことにより、単純型表皮水疱症の治療において重要な知見を得ることができた。

Report

(2 results)
  • 2023 Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (2 results)

All 2022

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Cargo receptor Surf4 regulates endoplasmic reticulum export of proinsulin in pancreatic β-cells.2022

    • Author(s)
      Saegusa K, Matsunaga K, Maeda M, Saito K, Izumi T, Sato K.
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 458-458

    • DOI

      10.1038/s42003-022-03417-6

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 複数のRab27エフェクターExophilinsが制御する,インスリン顆粒開口放出機構2022

    • Author(s)
      趙クンリ、松永耕一、水野公一、王昊、奥西勝秀、泉 哲郎
    • Organizer
      第65回日本糖尿病学会年次学術集会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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