Membrane Bound Mucins in Salivary Glands and Saliva

描述（由申请方提供）：粘蛋白是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合成和分泌。迄今为止，已经鉴定了13种不同的粘蛋白基因，并且这些粘蛋白基因可以分为两个不同的类别，凝胶形成粘蛋白和膜结合粘蛋白。在唾液分泌物中，粘蛋白促进说话和吞咽，保护口腔表面免受微生物、化学和机械损伤，并有助于在下面的表面和外部环境之间形成选择性渗透的扩散屏障。这些功能在很大程度上归因于唾液中主要的凝胶形成粘蛋白MG 1。然而，我们最近发现，两个膜结合粘蛋白，MUC1和MUC4，表达在所有主要的唾液腺，包括腮腺。虽然几乎没有什么是已知的唾液腺和唾液中的膜结合粘蛋白的表达和功能特性，我们的假设是，这些分子形成口腔宿主防御系统的一个组成部分，在保护口腔上皮表面。本项目的总体目标是了解这种情况发生的机制。 本研究的具体目的是：1）确定膜结合粘蛋白MUC1和MUC4在大、小唾液腺和不同腺体分泌物中的表达模式。2)表征膜结合粘蛋白和凝胶形成粘蛋白之间的相互作用的性质和3）研究MUC 1和MUC 4在保护口腔上皮表面免受微生物侵袭中的作用。

DESCRIPTION (provided by applicant): Mucins are heavily glycosylated proteins, which are synthesized and secreted by epithelial cells lining the gastrointestinal, respiratory and genitourinary tracts. To date, thirteen distinct mucin genes have been identified and these can be divided into two distinct classes, gel-forming mucins and membrane-bound mucins. In salivary secretions, mucins facilitate speech and swallowing, protect oral surfaces against microbial, chemical and mechanical injury and contribute to a selectively permeable diffusion barrier between underlying surfaces and the external environment. These functions have largely been attributed to the major gel-forming mucin in saliva, MG1. Nevertheless, we have recently shown that two membrane-bound mucins, MUC1 and MUC4, are expressed in all major salivary glands, including the parotid glands. While virtually nothing is known about the expression and functional properties of membrane-bound mucins in salivary glands and saliva, our hypothesis is that these molecules form an integral part of the oral host-defense system in the protection of oral epithelial surfaces. The overall goal of this project is to understand the mechanisms by which this occurs. The Specific Aims of this project are to: 1) determine the expression pattern of the membrane-bound mucins MUC1 and MUC4 in major and minor salivary glands and in different glandular secretions. 2) characterize the nature of the interactions between membrane-bound and gel-forming mucins and 3) investigate the role of MUC I and MUC4 in protection of oral epithelial surfaces from microbial attack.