Biology of mammalian Sialidases

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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.