Biology of mammalian Sialidases

哺乳动物唾液酸酶的生物学

• 批准号: RGPIN-2020-07215
• 负责人: Igdoura, Suleiman
• 金额: $ 2.33万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=718737
• 关键词: Biology; mammalian; Sialidases

Sialidases are found in viruses, bacteria, fungi, avians and mammals. Mammalian sialidases differ in their specificity, pH optimum, subcellular localization and tissue expression. To date, four genes encoding sialidases (neu1-4) have been cloned. The overall objective of my program is to investigate the cellular role of sialylation in biological systems. Defining the functional impact of sialidases on complex physiological and cellular processes should uncover the biological significance of sialidase-susceptible sialic acids on glycoproteins and glycolipids. The short term objective of this proposal is: (1) To characterize the mouse neu4 promoter and their functional cisacting elements in vitro. (2) To investigate the impact of NEU4 sialidase on muscle differentiation. (3) To investigate the intracellular localization and trafficking of NEU4. (4) To characterize the functional impact of NEU4 on sialylation of potential target molecules. Modulation of NEU4 expression may be essential not only for the breakdown of sialylated glycoconjugates but also in the activation or inactivation of functionally important events during muscle differentiation. The proposed studies should define the molecular mechanisms that regulate NEU4 expression, function and transport. Transcriptional control of the sialidase gene family and their functional roles will define the impact of the turnover or modification of many sialylated targets on a vast array of biological functions.

唾液酸酶存在于病毒、细菌、真菌、鸟类和哺乳动物中。哺乳动物唾液酸酶在特异性、最适 pH 值、亚细胞定位和组织表达方面有所不同。迄今为止，四个编码唾液酸酶（neu1-4）的基因已被克隆。我的项目的总体目标是研究唾液酸化在生物系统中的细胞作用。定义唾液酸酶对复杂的生理和细胞过程的功能影响应该揭示唾液酸酶敏感的唾液酸对糖蛋白和糖脂的生物学意义。该提案的短期目标是： (1) 体外表征小鼠 neu4 启动子及其功能性顺式作用元件。 (2)探讨NEU4唾液酸酶对肌肉分化的影响。 (3)研究NEU4的细胞内定位和运输。 (4) 表征 NEU4 对潜在靶分子唾液酸化的功能影响。 NEU4 表达的调节不仅对于唾液酸化糖复合物的分解至关重要，而且对于肌肉分化过程中功能性重要事件的激活或失活也至关重要。拟议的研究应明确调节 NEU4 表达、功能和运输的分子机制。唾液酸酶基因家族的转录控制及其功能作用将定义 许多唾液酸化靶点的更新或修饰对大量生物功能的影响。