REGULATION OF MUCIN GLYCOPROTEIN BIOSYNTHESIS

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Epithelial surfaces are protected by a slimy, visco-elastic coat termed mucus. This layer is the first line of defense against mechanical, microbial or chemical insult to the underlying tissues. Of particular functional significance are the highly glycosylated, mucin-glycoproteins. These molecules are responsible for the unique rheological properties of the mucus coat. Many of the symptoms which characterize xerostomia including mucosal ulceration, increased incidences of plaque mediated disease and atypical oral infections have been linked to either a quantitative lack of or qualitative change in salivary mucin. Our approach to this problem has been to study the regulation of normal mucin- glycoprotein biosynthesis. In this way we hope to gain insight into the mechanisms which may underlie specific forms of salivary dysfunction. We propose to: (1) construct and characterize cDNAs which code for the protein core of rat submandibular gland mucin- glycoprotein (MG), (2) determine levels of mRNA coding for the apo-mucin and the glutamine/glutamic acid rich proteins (GRP), which are another class of abundant proteins found in the rat submandibular gland, (3) define the biosynthetic pathway for both the MG and GRP and, (4) continue clarification of the structure and organization of genes which code for the GRP.