2021 Fiscal Year Final Research Report
Physiological function analysis of GOMED, a novel proteolytic degradation mechanism
| Project/Area Number |
19K07382
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | オートファジー / ゴルジ体 |
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| Outline of Final Research Achievements |
Golgi membrane-associated degradation pathway (GOMED) is an Atg5/Atg7-independent type of autophagy that contributes to the degradation of the accumulated proteins when the transport of proteins from the Golgi to the extracellular or plasma membrane is impaired. Analysis of the GOMED-1, a molecule essential for GOMED revealed that GOMED-1 localizes from the cytoplasm to the trans-Golgi and regulates the formation of isolation membranes from trans-Golgi membranes. Furthermore, brain-specific GOMED-1-deficient mice show that abnormal accumulation of ceruloplasmin, an iron transport protein and a degradation substrate of GOMED, resulting in neurodegenerative disease-like symptoms from iron deposition. These indicate that GOMED-1 functions to maintain neuronal cells via mechanisms different from those of canonical autophagy.
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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GOMED-1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、神経細胞を取り上げ、GOMEDが生体機能維持に不可欠な機能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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