This is a Program Project to continue investigation of the function and trafficking of specific liver cell! surface membrane proteins. Four projects involving 12 faculty investigators representing ten academic departments are proposed. The first Project will characterize specific cellular components mediating vesicle trafficking and sorting. Endosomal vesicles at specific stages of the endocytic pathway as well as exocytosing Herpes simplex vesicles will be examined. Our recent development of novel fluorescence microscopy technologies should greatly facilitate these studies. The second Project has characterized genomic regulators of connexin 32, and has recently demonstrated interactions between connexins and tight junction proteins. Interactions with the three other Projects regarding connexin trafficking continue. The third Project is focused on the isolation and characterization of trafficking mutants in the endocytic pathway. The Trfi mutant is the original trafficking mutant that we isolated. The gene that complements this mutation has been cloned and encodes a novel Casein Kinase II catalytic subunit. A second mutant cell line has been isolated, and protocols are proposed for isolation of additional lines. The trafficking defects of Trfl have been important tools for collaborative studies with the other Projects. The fourth Project is new and is focused on hepatocellular membrane trafficking in reverse cholesterol transport. Roles for caveolin and for phosphatidylcholine transfer protein in this process will be examined. This Project was added to the Program because of collaborations that developed with the existing three Projects. This Program also provides two Core facilities. The Administrative and Supporting Services Core provides the necessary secretarial, bookkeeping, and common equipment functions. The Molecular Cytology Core provides cytochemical and morphologic services. All of these Projects are concerned with interrelated areas of hepatocyte membrane biology and pathobiology. The expertise of the investigators is complementary, and the ability to work and interact within the framework of a Program promotes the sharing of ideas, methodology, and resources.
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