Structure and Function of Human Salivary Mucins

描述：在颌下腺、舌下腺和小涎腺的分泌物中存在两种截然不同的粘蛋白，一种是形成粘蛋白MG1的大的多聚体凝胶，另一种是名为MG2的小单体粘蛋白。MG1似乎是两种粘蛋白基因产物MUC5B和一种新发现的粘蛋白MUC19的混合物。MG2似乎含有单一的粘蛋白基因产物MUC7。粘蛋白保护口腔表面不干燥，润滑硬组织和软组织以促进咀嚼、说话和吞咽，并在底层上皮表面和外部环境之间形成选择性渗透的扩散屏障。我们已经证明了MG1和MG2都与其他唾液蛋白形成了异型复合体，并假设以前归因于粘蛋白的许多功能可以归因于它们复杂伙伴的性质。这个项目的总体目标是了解唾液和全唾液中粘蛋白和粘蛋白复合体的分子组成如何影响它们在口腔中的生物学功能。该项目的具体目标是： 1)利用基于质谱学的蛋白质组学方法鉴定与MG1形成复合体的唾液蛋白质； 2)分离和鉴定与镁离子相互作用的唾液蛋白； 3)通过测定复合体的特定生物学性质，探索粘蛋白复合体的功能性质； 4)研究在哺乳动物细胞系中表达的凝胶形成粘蛋白的组装机制；以及 5)用捕获ELISA测定全唾液和唾液中凝胶形成粘蛋白的分子组成和分泌模式。

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.