TFF-petides and their mechanisms of action during cell migration

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Trefoil factors (TFFs) represent a family of secreted polypeptides recently identified in mammalians and Xenopus that in adult mammalian organisms are expressed mainly in tissues of the gastrointestinal tract. Studies of TFF function have identified TFFs as motogens acting in early processes of epithelial restitution when cells rapidly migrate from the margins of the damaged region over the denuded area to reestablish epithelial continuity. In this project the cellular and molecular mechanisms responsible for the induction of migration by trefoil peptides shall be examined. First, the influence of TFFs on the cadherin-catenin adhesion complex during migration will be analyzed by biochemical analysis and immunofluorescence microscopy. Second, it shall be adressed whether apical glycoproteins such as DF3/MUC1 play a role as TFF receptors and whether binding of TFF to these glycoproteins is a regulatory link to the cadherin-catenin system. Furthermore, it shall be adressed whether the motogenic activity of trefoil peptides is also mediated by basolateral receptors. Third, employing differential cDNA analysis (cDNA arrays) and high-resolution 2D-gelelectrophoresis, TFF induced changes in gene expression and posttranslational modifications of signaling proteins shall be identified and tested for their relevance in induction of cell migration.