Two types of epithelial cell-cell junctions, desmosomes and adherens junctions, are important in maintaining the integrity of epithelium. Disruption of epidermal junctions results in inherited and acquired blistering diseases, but the mechanisms of the disruption are unknown. To learn more about component proteins and assembly of structurally important junctions, we have purified proteins from preparations of mammalian junctions from pig oral epithelium. One, a 37 kDa protein, has been cloned and sequenced and has been found to be highly homologous with a family of lectins, proteins with the ability to bind carbohydrates, in different species; no other junction protein has been found to be a member of this family of proteins. Studies with antibodies to the protein suggest strongly that the protein is present in adherens junctions and indicate that the protein has a restriction previously undescribed for junction proteins (a) primarily to the oral epithelium and (b) to only suprabasal cells within that epithelium. In other studies, we have also demonstrated for the first time the presence of adherens junctions in mammalian epidermis and have shown that these junctions are present in human skin. We plan to continue studies of adherens junctions in human skin and to further delineate the location of the 37 kDa probable adherens junction protein in epithelium. Since the cDNA sequence and amino acid sequence are highly homologous with a mammalian lectin, which binds lactose, we will determine whether the 37 kDa protein can bind to sugars, especially lactose. We will identify proteins to which this protein binds in junctions and will attempt to find and clone the cDNA for the human protein corresponding to the 37 kDa protein. To understand the structure of the gene for the 37 kDa protein and thereby relate it to a correlative human gene, we will clone and sequence the genomic DNA for the pig gene. Finally we will continue to define the structure and possible function of adherens junctions in human tissues with available antibodies and will use organ culture in an effort to upregulate these junctions. These studies will elucidate the structure and function of epithelial junctions and may demonstrate a new function, the binding of carbohydrate, in a structural protein of epithelial junctions. These studies will increase our understanding of the structure and function of these junctions and of their assembly from component proteins.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Method to Extend Research in Time (MERIT) Award (R37)
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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