2024 Fiscal Year Final Research Report
Elucidation of the Molecular Mechanism of GOMED and Its role in the pathogenesis of neurodegenerative diseases
| Project/Area Number |
22K06909
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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 49010:Pathological biochemistry-related
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| Research Institution | Institute of Science Tokyo (2024)
Tokyo Medical and Dental University (2022-2023) |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Keywords | タンパク分解 / 神経変性 / ゴルジ体 |
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| Outline of Final Research Achievements |
The Golgi-membrane-associated degradation (GOMED) pathway is a physiological mechanism that mediates the degradation of proteins whose trafficking from the Golgi apparatus to the plasma membrane or extracellular space is impaired. In this study, we identified Wipi3 as an essential effector molecule of the GOMED pathway. Furthermore, it was demonstrated that: (1) Wipi3 undergoes dephosphorylation upon induction of GOMED; (2) this dephosphorylation is critical for the execution of GOMED; and (3) the phosphatase responsible for Wipi3 dephosphorylation was identified. These findings reveal that regulation of Wipi3 dephosphorylation is indispensable for the activation of the GOMED pathway.
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| Free Research Field |
細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
GOMEDを制御する分子Wipi3の解析から、GOMEDの分子機構の一端を理解することができた。また、Wipi3の脱リン酸化制御が、GOMED実行に不可欠であることを示すことができた。GOMEDは分泌経路を遮断するときに誘導される機構であることを勘案すると、分泌を行っている細胞を中心に、多岐にわたる細胞で重要な役割を果たしているものと考えられる。また、糖尿病や神経変性疾患などの多くの疾患の発症に関わっている可能性が考えられる。従って、本研究は、様々な疾患の病態生理解明や疾患治療に波及効果をもたらすと期待される。
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