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.
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