Molecular mechanism and functional significance of the regulation of ectodomain shedding by alternative splicing
| Project/Area Number |
18K06911
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Ritsumeikan University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 細胞外領域シェディング / 選択的スプライシング / 接着分子 / 酸性アミノ酸 / ALCAM / 負電荷アミノ酸 / Unc5b / シェディング / ADAMファミリー |
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| Outline of Final Research Achievements |
Ectodomain shedding (shedding) is a post-translational modification mechanism that cleaves a membrane protein in the vicinity of the membrane and solubilizes the extracellular region. In this study, through analysis of the adhesion molecule ALCAM, whose shedding susceptibility changes depending on the presence or absence of alternative exon encoding the vicinity of the membrane, it was clarified that acidic amino acids encoded by the selective exon are required for conferring shedding resistance. Furthermore, it was clarified that the number of acidic amino acids is important, not the position, and that shedding resistance can be imparted even if acidic amino acids are introduced into other membrane proteins.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、膜タンパク質のシェディング感受性が「有利な条件の存在」ではなく「不利な条件の不在」によって規定されることが示唆された。この知見は、これまで明らかにされていなかったシェディングの特異性決定機構の理解を大きく進めるものである。またシェディングは炎症性疾患・がん・神経変性疾患などの発症に関わることが知られており、シェディングに不利な条件（＝酸性アミノ酸）の発見はこれらの疾患の治療方法の開発に繋がる可能性がある。
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Report
(4 results)
Research Products
(17 results)
