Demonstration of the vertebrate CMP-sialic acid synthetase as a novel regulatory protein of neural cell apoptosis
| Project/Area Number |
21K15040
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 43030:Functional biochemistry-related
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| Research Institution | Nagoya University |
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Principal Investigator |
Wu Di 名古屋大学, 糖鎖生命コア研究所, 助教 (10817547)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | CMP-Sia synthetase / apoptosis / medaka fish / Apoptosis / Sialylation / CSS / neurogenesis / medaka / Sia-glycoconjugates |
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| Outline of Research at the Start |
CMP-sialic acid synthetase (CSS) is a key enzyme for the expression of Sia-Glycolconjugates on the cell surface. Our previous results suggest that CSS plays a critical role in neurogenesis, not only as a sialylation-involved enzyme but also as an apoptosis-related protein. To clarify how CSS regulates the neural cell apoptosis: (1) To identify protein X by the proximity labeling technique; (2) To characterize the interaction between protein X and CSS at the molecular level; (3) To clarify the significance of the protein X-CSS interaction at the animal level using medaka model.
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| Outline of Final Research Achievements |
CMP-sialic acid synthetase (CSS) is a key enzyme in sialic acid metabolism. However, medaka with a point mutation in the N-domain of CSS (named MuN) were lethal at early developmental stage due to cardiomyopathy and abnormal apoptosis in neural cells without affecting the sialylation state. To clarify the mechanism, we studied on the interacting proteins of CSS in mouse neuroblastoma cell line (Neuro2A). As a result, various interacting proteins of CSS in Neuro2A cell were confirmed, including Fragile X related protein (FXRP), which is the key protein caused apoptosis in MuN medaka.
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| Academic Significance and Societal Importance of the Research Achievements |
MuN mutant medaka is a perfect model, since it showed abnormal apoptosis in neural system and cardiomyopathy. It is also the first time to target on the interacting proteins of CSS. This study is important to understand the pathophysiological mechanism of Sia metabolism-related diseases.
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Report
(3 results)
Research Products
(16 results)
