REGULATION OF HUMAN SALIVARY MUCIN GLYCOSYLATION

人类唾液粘蛋白的明显机械贡献，凭借 在脱辅基蛋白核心周围密集排列的糖聚糖，以保护和 口腔软组织的润滑性早已被人们认识到。更多 最近的研究表明，唾液粘蛋白具有额外的能力 通过直接调节口腔的生物环境 与口腔细菌的相互作用。糖链结构与镁离子的结合 (MUC7)，人类低分子量唾液粘蛋白，特异性 细菌受体已被牵连。 SAAlpha2、3Ga1Beta1、3GalNAC-Chains以及另外两种Core 1类型 链，Fucalpha1，2Ga1Beta1，3GalNAc-及其共同的前体。 Ga1Beta1，3GalNAC-，构成了Mg2上糖链的主要部分。 MG2的两种主要亚型，MG2a和MG2b已被记录在案；它们是 推测是由唾液酸化的AND的差异表达产生的 岩藻糖化-核心1低聚糖。 作为了解分子和细胞因素的第一步， 口述人唾液粘蛋白中的多糖组成，生物合成 镁2上的唾液酸化和岩藻糖化的核心1寡糖将是 仔细检查了一下。第一步将是分子 通过对cDNA和基因组序列的分析，鉴定了该病毒 同源糖基转移酶、α2，3-唾液酸基转移酶和 α1，2-岩藻糖基转移酶。分子探针产生的结果是 这些研究将被用来检验核心的差异合成 1低聚糖。镁2异构体产生的可能性是 不同亚群的分泌细胞表达不同水平 唾液酸基转移酶和岩藻糖基转移酶的 原位杂交法。此外，在每个单元格中 表达岩藻糖基转移酶和唾液酸基转移酶，潜在的竞争 这些酶之间的共同底物可能会决定最终 唾液酸化和岩藻糖化结构的比率。这种可能性，就像 以及无粘蛋白一级结构对差异的影响 糖基化，将通过转染和表达的方式进行检测 脱蛋白粘蛋白和糖基转移酶序列。最后，我们将努力 用来鉴定唾液腺来源的细胞系 调节粘蛋白的表达。这些代码行最终将在 调控无粘蛋白和无粘蛋白的分子解剖 糖基转移酶在唾液腺中的表达。

The obvious mechanical contributions of human salivary mucins, by virtue of glycans densely packed around apoprotein cores, to protection and lubrication of oral cavity soft tissues have long been recognized. More recent studies demonstrated the additional ability of salivary mucins to modulate the biological environment of the oral cavity by direct interaction with oral bacteria. Binding of glycan structures on MG2 (MUC7), the human low molecular weight salivary mucin, to specific bacterial receptors have been implicated. SAalpha2,3Ga1Beta1, 3GalNAC- chains, along with two other Core 1 type chains, Fucalpha1,2Ga1Beta1,3GalNAc- and their common precursor. Ga1Beta1,3GalNAC-, comprise the major proportion of glycan chains on MG2. Two major isoforms of MG2, MG2a and MG2b, have been documented; these are putatively generated by differential expression of the sialylated- and fucosylated-Core 1 oligosaccharides. As a first step in understanding the molecular and cellular factors that dictate glycan composition in human salivary mucins, the biosynthesis of the sialylated- and fucosylated-Core 1 oligosaccharides on MG2 will be examined in detail. The first step will be the molecular characterization, by analysis of cDNA and genomic sequences, of the cognate glycosyltranferases, the alpha2,3-sialyltransferase and the alpha1,2-fucosyltransferase. Molecular probes generated as a result of these studies will be used to examine differential synthesis of the Core 1 oligosaccharides. The possibility that the MG2 isoforms result from different sub-populations of secretory cells expressing different levels of the sialytransferase and fucosyltransferase will be addressed by the in situ hybridization approach. Furthermore, within each cell that expresses both the fucosy- and sialytransferases, potential competition between these enzymes for the common substrate may dictate the final ratio of sialylated and fucosylated structures. This possibility, as well as the influence of apomucin primary structure on the differential glycosylation, will be examined by means of transfection and expression of apomucin and glycosyltransferase sequences. Finally, efforts will be made to identify cell lines of salivary gland origin that retain regulated mucin expression. These lines will be ultimately useful in the molecular dissection of pathways that regulate apomucin and glycosyltransferase expression in salivary glands.