Membrane Bound Mucins in Salivary Glands and Saliva

粘蛋白是一种高度糖基化的蛋白质，由胃肠道上皮细胞分泌， 呼吸道和泌尿生殖道。已经鉴定了两类不同的粘蛋白，凝胶形成粘蛋白 和分泌的粘蛋白。在口腔中，形成凝胶的粘蛋白促进说话和吞咽，保护口腔， 表面，并有助于在下面的上皮细胞和细胞之间的选择性渗透扩散屏障。 外部环境我们已经表明，膜粘蛋白也表达在唾液腺和口腔粘膜中。 并提出这些粘蛋白可以在口腔上皮表面形成支架， 形成粘蛋白和其他唾液蛋白可以选择性地结合。绑定可以用来集中这些 蛋白质的特定区域，并可以延长其在口腔中的停留时间。看来， 支架将是口腔宿主防御系统的关键组成部分， 细菌、化学和机械损伤。膜结合粘蛋白含有两个非共价缔合的 亚基：一个粘蛋白样细胞外亚基和一个细胞质亚基， 信号装置.我们的假设是，支架中的膜结合粘蛋白的功能是 受体分子，将细胞外部条件的信息转化为基因的变化， 宿主反应的表达和激活。这一过程可能涉及以下方面的特定相互作用： 膜结合粘蛋白和支架的其他组分。本建议的具体目的是：1） 研究膜结合粘蛋白和分泌唾液粘蛋白之间的相互作用，2）鉴定非- 与膜结合粘蛋白形成复合物并绘制相互作用结构域的粘蛋白蛋白，3） 表征粘蛋白支架的所有组分在细菌损伤模型中的作用，以及4）研究 这两种粘蛋白亚基在感受细菌攻击和激活 细胞内信号通路。 本研究的重点是口腔黏膜表面粘蛋白有序支架的表征， 上皮细胞及其与口腔细菌的相互作用。这些相互作用可能代表新的治疗靶点， 治疗或预防口腔感染和牙周病。

Mucins are heavily glycosylated proteins which are secreted by epithelial cells lining the gastrointestinal, respiratory and genitourinary tracts. Two distinct classes of mucins have been identified, gel forming mucins and secreted mucins. In the oral cavity, gel forming mucins facilitate speech and swallowing, protect oral surfaces, and contribute to a selectively permeable diffusion barrier between underlying epithelia and the external environment. We have shown that membrane mucins are also expressed in salivary glands and oral epithelia and have proposed that these mucins may form a scaffold on oral epithelial surfaces to which gel forming mucins and other salivary proteins can selectively bind. Binding could serve to concentrate these proteins in specific regions and could prolong their residence time in the oral cavity. It seems likely that the scaffold would be a key component of the oral host defense system in protection of epithelial surfaces from bacterial, chemical and mechanical injury. Membrane bound mucins contain two non-covalently associated subunits: a mucin-like extracellular subunit and a cytoplasmic subunit which is involved in intracellular signalling. Our hypothesis in this proposal is that the membrane bound mucins in the scaffold function as receptor molecules, translating information about conditions on the outside of the cell into changes in gene expression and activation of a host response. This process likely involves specific interactions between membrane bound mucins and other components of the scaffold.The Specific Aims of this proposal are to: 1) investigate interactions between membrane bound mucins and secreted salivary mucins, 2) identify non- mucin proteins which form complexes with membrane bound mucins and map the interacting domains, 3) characterize the role of all components of the mucin scaffold in a model of bacterial injury and 4) investigate the functional capacity of role of both mucin subunits in sensing a bacterial challenge and activation of intracellular signalling pathways. This proposal is focused on the characterization of the ordered mucin scaffold on the surface of oral epithelial cells and its interactions oral bacteria. These interactions may represent new therapeutic targets to treat or prevent oral infections and periodontal disease.