Demonstration of the vertebrate CMP-sialic acid synthetase as a novel regulatory protein of neural cell apoptosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15040
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Nagoya University
• Principal Investigator: Wu Di 名古屋大学, 糖鎖生命コア研究所, 助教 (10817547)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: CMP-Sia synthetase / apoptosis / medaka fish

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.

Free Research Field

機能生物化学関連

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.