Cytoskeletal-transmembrane glycoprotein interactions have an important role in various cellular functions, including cell growth, cell adhesion, and signal transduction. Several proteins mediate the interactions of the cytoskeleton with proteins and structures on the cell membrane. ERM proteins (ezrin, moesin and radixin) are a newly found family postulated to be membrane- cytoskeleton linkers. The mutation and perturbations in the cytoskeletal-membrane linker proteins, including ERM proteins, may disturb normal cell adhesion. In this way the cells could obtain tumorigenic properties. We propose to study whether transmembrane glycoproteins such as the cell adhesion molecule C-CAM 105, the heparin sulfate proteoglycan syndecan-1, and the epithelial mucin MUC1 are associated with cytoskeletal anchorage proteins or other ERM proteins. The cytoplasmic tails of transmembrane glycoproteins will be used in affinity chromatography studies to detect interacting protein in metabolically labeled cell lysates. The identified interactions will be studied with purified proteins and the binding sites on these proteins will be characterized. The association of ezrin with transmembrane glycoproteins will also be studied by transfection of ezrin cDNA into cultured cells to determine whether ezrin redistributes the transmembrane glycoproteins and the determination of the molecular determinants of protein interactions will clarify the role of ezrin or other cytoskeletal molecules in the function of C-CAM 105, MUC1, and syndecan-1.
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