Membrane Bound Mucins in Salivary Glands and Saliva

粘蛋白是一种高度糖化的蛋白质，由胃肠道衬里的上皮细胞分泌， 呼吸道和泌尿生殖道。已鉴定出两种截然不同的粘蛋白，凝胶形成粘蛋白 并分泌粘液。在口腔中，凝胶形成的粘液有助于说话和吞咽，保护口腔 表面，并有助于在底层上皮和表面之间形成选择性可渗透的扩散屏障 外部环境。我们已经证明，唾液腺和口腔中也有膜粘蛋白的表达。 上皮细胞，并提出这些粘蛋白可能在口腔上皮细胞表面形成支架，凝胶到 形成粘蛋白和其他唾液蛋白可以选择性结合。绑定可以用来集中这些 蛋白质在特定区域，并可延长其在口腔中的滞留时间。看起来很可能是 支架将是口腔宿主防御系统的关键组成部分，以保护上皮表面免受 细菌、化学和机械损伤。膜结合的粘蛋白含有两个非共价结合的 亚基：一个粘蛋白样胞外亚单位和一个参与细胞内的胞内亚基 发信号。我们在这个建议中的假设是，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变化 表达和激活宿主反应。这一过程可能涉及到 膜结合粘蛋白和支架的其他成分。这项提议的具体目的是：1) 研究膜结合粘蛋白和分泌的唾液粘蛋白之间的相互作用，2)鉴定非 与膜结合的粘蛋白形成复合体并绘制相互作用结构域的粘蛋白蛋白，3) 描述粘蛋白支架的所有成分在细菌损伤模型中的作用，并研究 两种粘蛋白亚基在感受细菌挑战和激活过程中的功能 细胞内信号通路。 本研究的重点在于口腔表面有序粘蛋白支架的表征。 口腔细菌上皮细胞及其相互作用。这些相互作用可能代表着新的治疗靶点 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.