Membrane Bound Mucins in Salivary Glands and Saliva

唾液腺和唾液中的膜结合粘蛋白

基本信息

批准号：
7178530
负责人：
GWYNNETH D OFFNER
金额：
$ 29.18万
依托单位：
BOSTON MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-04-01 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7178530
关键词：
Activities of Daily Living Architecture Bacterial Model Binding Biological Assay Cell Line Cell surface Cells Chemical Injury Chemicals Class Co-Immunoprecipitations Complex Condition Cues Deglutition Diffusion Dissociation Environment Enzymes Epithelial Epithelial Cells Epithelium Far-Western Blotting Gel Gene Expression Genes Genitourinary system Glutathione S-Transferase Host Defense Immune response Inflammatory Injury MUC5B gene Maps Mass Spectrum Analysis Mechanics Mediator of activation protein Membrane Microbe Molecular Molecular Weight Mucin-1 Staining Method Mucin-2 Staining Method Mucins Oral Oral cavity Periodontal Diseases Play Process Property Proteins Research Personnel Role Saliva Salivary Salivary Glands Salivary Proteins Signal Pathway Signal Transduction Site Speech Structure Surface System Thinking Time Translating base concept extracellular gastrointestinal microbial novel therapeutics oral bacteria oral cavity epithelium oral infection prevent programs receptor residence respiratory response salivary mucins scaffold therapeutic target yeast two hybrid system

项目摘要

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.

描述（由申请人提供）：粘蛋白是大量的糖基化蛋白，由胃肠道，呼吸道和泌尿生殖道的上皮细胞分泌。已经鉴定出两种不同类别的粘蛋白，凝胶形成粘蛋白和分泌的粘蛋白。在口腔中，形成粘蛋白的凝胶有助于语音和吞咽，保护口腔表面，并有助于有选择性的渗透性扩散屏障与潜在的上皮和外部环境之间。我们已经表明，膜粘蛋白在唾液腺和口服上皮中也表达，并提出这些粘蛋白可能在口服上皮表面上形成支架，形成粘液和其他唾液蛋白可以选择性地结合。结合可以用来将这些蛋白质集中在特定区域，并可以延长其在口腔中的停留时间。脚手架似乎是保护上皮表面免受细菌，化学和机械损伤的口服宿主防御系统的关键组成部分。膜结合的粘蛋白包含两个无共价相关的亚基：粘蛋白样细胞外亚基和一个参与细胞内信号传导的细胞质亚基。在此应用中，我们的假设是支架中的膜结合粘蛋白作为受体分子，将有关细胞外部条件的信息转化为基因表达的变化和宿主反应的激活。这个过程可能涉及膜结合的粘蛋白与支架的其他成分之间的特定相互作用。该应用的具体目的是：1）调查膜结合的粘蛋白和分泌的唾液粘蛋白之间的相互作用，2）确定与膜结合的粘蛋白形成复合物的非粘蛋白蛋白，并绘制相互作用的结构域，3）表征粘膜骨scap虫的所有成分的作用，并在细菌损伤模型中进行粘液型的作用，4）粘膜的作用。细胞内信号通路的激活。该应用集中在口腔上皮细胞表面上有序的粘蛋白支架及其相互作用的口腔细菌的表征。这些相互作用可能代表了治疗或预防口腔感染和牙周疾病的新治疗靶标。