Membrane Bound Mucins in Salivary Glands and Saliva

性状（由申请方提供）：粘蛋白是一种高度糖基化的蛋白质，由胃肠道、呼吸道和泌尿生殖道的上皮细胞分泌。已经鉴定了两种不同类别的粘蛋白，凝胶形成粘蛋白和分泌粘蛋白。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外部环境之间形成选择性渗透的扩散屏障。我们已经表明，膜粘蛋白也表达在唾液腺和口腔上皮细胞，并提出这些粘蛋白可以形成口腔上皮表面的凝胶形成粘蛋白和其他唾液蛋白可以选择性结合的支架。结合可以使这些蛋白质集中在特定区域，并可以延长它们在口腔中的停留时间。这似乎是可能的支架将是口腔宿主防御系统的关键组成部分，在保护上皮表面免受细菌，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：粘蛋白样细胞外亚基和参与细胞内信号传导的细胞质亚基。我们在本申请中的假设是支架中的膜结合粘蛋白作为受体分子起作用，将细胞外部条件的信息翻译成基因表达的变化和宿主反应的激活。该过程可能涉及膜结合粘蛋白和支架的其他组分之间的特异性相互作用。本申请的具体目的是：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）鉴定与膜结合粘蛋白形成复合物的非粘蛋白蛋白并绘制相互作用结构域，3）表征粘蛋白支架的所有组分在细菌损伤模型中的作用，以及研究两种粘蛋白亚基在感受细菌挑战和激活细胞内信号传导途径中的功能能力。本论文主要研究口腔上皮细胞表面粘蛋白有序支架的结构特征及其与口腔细菌的相互作用。这些相互作用可能代表治疗或预防口腔感染和牙周病的新的治疗靶点。

DESCRIPTION (provided by applicant): 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 signaling. Our hypothesis in this application 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 application 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 signaling pathways. This application 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.