Function of receptor mediated endocytosis in Hydra morphogenetic signaling

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The overall aim of this study is to understand the role of membrane trafficking in morphogenetic signaling. For the morphogen Notch endocytosis is essential for signaling and also for Wnt signaling several studies let presume that receptor mediated endocytosis is necessary for signal transduction. The function of endocytosis in Wnt signaling will be analyzed in this study and differences in endo- and exocytosis of canonical and noncanonical Wnt ligands in Hydra will be examined. Hydra is an ancient and very simple multicellular system that posses, however, an almost complete set of Wnt genes, otherwise only known from vertebrates. Despite their crucial function in embryogenesis, cell differentiation and cancer, the mechanisms of ligand uptake and processing are only poorly understood so far. Based on Hydra’s simple body plan and its clear patterns of differentiated cells, major insights into the dynamics and function of morphogen-related membrane trafficking are expected. The first aim is to clarify the secretory route of Wnt ligands and receptors along the secretory pathway to the exocytosis at the plasma membrane. The second aim of this study is to analyze the endocytotic route these proteins take: clathrin mediated or clathrin independent endocytosis? The cellular and molecular fate after binding of Wnt to its receptor is a major topic of this project. To investigate the mechanism of receptor mediated endocytosis of Wnt, patch clamp capacitance measurements on isolated Hydra cells are used. They allow the direct measurement of endo- and exocytosis at the plasma membrane of living cells. This work will not only increase our knowledge of the role of membrane trafficking in Wnt signaling but also provide information about the mechanisms involved in receptor mediated endocytosis of morphogens in general. Considering the importance of Wnt signaling in development, human diseases, and cancer, new insights in membrane trafficking of Wnt and interacting proteins are of major significance.