STRUCTURE AND FUNCTION OF HUMAN SALIVARY MUCINS

人唾液粘蛋白​​的结构和功能

• 批准号: 2903512
• 负责人: ROBERT F TROXLER
• 金额: $ 28.02万
• 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 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2903512
• 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

Salivary secretions contain two distinct mucins, a high molecular weight mucin named MG1 and a low molecular weight mucin named MG2. Mucins protect oral surfaces against desiccation, form a selectively permeable diffusion barrier between underlying surfaces and the external environment, lubricate hard and soft tissues to minimize mechanical injury, facilitate speech and swallowing and provide a physical barrier to protect against colonization of potentially harmful microbes and viruses. We have shown that MG1 is actually a mixture of mucin gene products, containing MUC4, MUC5B and a novel salivary mucin (NSM), whereas MG2 is a single gene product encoded in the MUC7 gene. MG1 and MG2 are differentially expressed in major and minor salivary glands and the overall goal of this project is to understand their structural features and functional properties. The specific aims of this project are to: 1. determine the structural organization and sequence of mucin gene products comprising MG1 by characterization of a novel salivary mucin (NSM) and elucidating the C-terminal sequence of MUC4. 2. investigate the biosynthesis and assembly of MUC4, MUC5B and NSM using mucin constructs expressed in COS-7 cells. 3. evaluate interactions of MG2 with oral microbes and investigate MG2 heterotypic complexes with other salivary proteins in the yeast two hybrid system. 4. study expression of trefoil peptides in major and minor salivary glands using immunohistochemistry and in situ hybridization. 5. examine MG1 and MG2 levels in salivary secretions and whole saliva and determine secretion profiles using mucin-specific capture ELISAs.

唾液分泌物含有两个不同的粘蛋白，一种称为MG1的高分子量粘蛋白和一个名为MG2的低分子量粘蛋白。 粘蛋白可防止口腔表面免受干燥，形成一个可选择性的渗透性扩散屏障与外部环境之间，润滑硬组织和软组织以最大程度地减少机械损伤，促进言语和吞咽，并为防止潜在的危害微生物和病毒的定殖提供一个物理障碍。 我们已经表明，MG1实际上是粘蛋白基因产物的混合物，其中含有MUC4，MUC5B和一种新型的唾液粘蛋白​​（NSM），而MG2是MUC7基因中编码的单个基因产物。 MG1和MG2在主要和次要的唾液腺中差异表达，该项目的总体目标是了解它们的结构特征和功能特性。该项目的具体目的是：1。通过表征新型唾液粘蛋白​​（NSM）并阐明MUC4的C末端序列，确定包含MG1的粘蛋白基因产物的结构组织和序列。 2。使用COS-7细胞中表达的粘蛋白构建体研究MUC4，MUC5B和NSM的生物合成和组装。 3。评估MG2与口腔微生物的相互作用，并研究MG2异型复合物与酵母两个杂种系统中其他唾液蛋白的相互作用。 4。使用免疫组织化学和原位杂交研究三叶肽在主要和小唾液腺中的表达。 5。检查唾液分泌物和整个唾液中的MG1和MG2水平，并使用粘蛋白特异性捕获ELISAS确定分泌谱。