Biology of mammalian Sialidases

唾液酸酶存在于病毒、细菌、真菌、鸟类和哺乳动物中。哺乳动物唾液酸酶的特异性、最佳pH值、亚细胞定位和组织表达不同。迄今为止，已经克隆了4个编码唾液酸酶（neu1-4）的基因。我的计划的总体目标是研究唾液化在生物系统中的细胞作用。确定唾液酸酶对复杂生理和细胞过程的功能影响，将揭示唾液酸对糖蛋白和糖脂的生物学意义。本课题的短期目标是：(1)在体外对小鼠neu4启动子及其功能顺化元件进行表征。(2)探讨NEU4唾液酸酶对肌肉分化的影响。(3)探讨NEU4在细胞内的定位和转运。(4)表征NEU4对潜在靶分子唾液化的功能影响。NEU4表达的调节可能不仅对唾液化糖缀合物的分解至关重要，而且对肌肉分化过程中重要功能事件的激活或失活也至关重要。今后的研究应明确NEU4表达、功能和转运调控的分子机制。唾液酸酶基因家族的转录控制及其功能作用将确定许多唾液酸化靶标的转换或修饰对大量生物功能的影响。

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.