Structure and Function of Human Salivary Mucins

人唾液粘蛋白​​的结构和功能

• 批准号: 6925678
• 负责人: GWYNNETH D OFFNER
• 金额: $ 32.77万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6925678
• 关键词: African American; caucasian American; chromosome translocation; enzyme linked immunosorbent assay; gene expression; human tissue; immunocytochemistry; in situ hybridization; messenger RNA; molecular weight; mucins; nucleotides; oral bacteria; protein binding; protein biosynthesis; protein protein interaction; protein sequence; protein structure function; racial /ethnic difference; reflux esophagitis; saliva; sublingual gland; submandibular gland; tissue /cell culture; yeast two hybrid system

DESCRIPTION: Two distinct mucins occur in the secretions of submandibular, sublingual and minor salivary glands, a large multimeric gel forming mucin named MG1 and a small monomeric mucin named MG2. MG1 appears to be a mixture of two mucin gene products, MUC5B and a newly identified mucin, MUC19. MG2 appears to contain a single mucin gene product, MUC7. Mucins protect oral surfaces against desiccation, lubricate hard and soft tissues to facilitate mastication, speech and swallowing and form a selectively permeable diffusion barrier between underlying epithelial surfaces and the external environment. We have shown that both MG1 and MG2 form heterotypic complexes with other salivary proteins and posit that many of the functions previously attributed to mucins can be ascribed to the nature of their complex partners. The overall goal of this project is to understand how the molecular composition of mucins and mucin complexes in salivary secretions and whole saliva affects their biological function in the oral cavity. The Specific Aims of this project are to: 1) Identify salivary proteins that form complexes with MG1 using a mass spectrometry based proteomics approach; 2) Isolate and identify salivary proteins that interact with MG2; 3) Explore the functional properties of mucin complexes using assays to measure the specific biological properties of complex partners; 4) Investigate the mechanism for assembly of gel-forming mucins expressed in mammalian cell lines; and 5) Determine the molecular composition and secretion patterns of gel forming mucins in whole saliva and salivary secretions using capture ELISAs.

描述：下颌下腺、舌下腺和小唾液腺的分泌物中存在两种不同的粘蛋白，一种是形成粘蛋白的大的多聚体凝胶，称为 MG1，另一种是小的单体粘蛋白，称为 MG2。 MG1 似乎是两种粘蛋白基因产物 MUC5B 和新鉴定的粘蛋白 MUC19 的混合物。 MG2似乎含有单一粘蛋白基因产物MUC7。粘蛋白保护口腔表面免受干燥，润滑硬组织和软组织以促进咀嚼、言语和吞咽，并在下面的上皮表面和外部环境之间形成选择性渗透的扩散屏障。我们已经证明 MG1 和 MG2 都与其他唾液蛋白形成异型复合物，并假设以前归因于粘蛋白的许多功能可以归因于其复合物伙伴的性质。该项目的总体目标是了解唾液分泌物和全唾液中粘蛋白和粘蛋白复合物的分子组成如何影响其在口腔中的生物学功能。该项目的具体目标是： 1) 使用基于质谱的蛋白质组学方法鉴定与 MG1 形成复合物的唾液蛋白； 2）分离并鉴定与MG2相互作用的唾液蛋白； 3) 通过测定复合物伴侣的特定生物学特性来探索粘蛋白复合物的功能特性； 4) 研究哺乳动物细胞系中表达的凝胶形成粘蛋白的组装机制；和 5) 使用捕获 ELISA 确定全唾液和唾液分泌物中凝胶形成粘蛋白的分子组成和分泌模式。