2022 Fiscal Year Annual Research Report
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 Institution | Nagoya University |
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Principal Investigator |
呉 迪 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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| Keywords | CMP-Sia synthetase / Apoptosis / Sialylation |
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| Outline of Annual Research Achievements |
CMP-sialic acid synthetase (CSS) is a key enzyme for the expression of sialic acid (Sia)-containing glycoconjugates on the cell surface. N-Domain of CSS is a catalytic domain, which containes the active site and 5 conserved motifs; 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 underlying mechanism of these phenomenon, I executed the following experiments: (1) To systematically analyze the differences between WT and MuN medaka, the RNA-Seq analysis was done on WT and homozygous MuN medaka fry at 8dpf. As a result, various proteases and the apoptosis inducers were obviously increased in homozygous MuN medaka fry.
(2) To understand the mechanism how MuN mdkCSS induced abnormal apoptosis during early developmental stages of medaka fry, the Fragile X related protein (FXRP), which mediates transport of specific mRNAs to different intracellular compartments and inhibit translation of their target mRNAs, was focused on. The interaction of FXRP with wild-type and MuN CSS was investigated using Neuro2A cells by immunoprecipitation (IP). Interestingly, wild-type CSS interacted with FXRP in Neuro2A cells, but MuN mdkCSS did not.
These results indicate that the unnusual apoptosis happens in heart and neural system of MuN medaka fry because of the impairment of interaction between mdkCSS and FXRP proteins.
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