Molecular Mechanisms of apoptosis in Hydra

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Apoptosis is an animal specific kind of programmed cell death, which is regulated by members of the Bcl-2 family and by caspases. These molecular pathways are conserved in all animals and even in prebilaterian animals, such as the cnidarian Hydra we could identify an extensive network of apoptotic proteins. Apoptosis can be induced from within the cell, e.g. by DNA damage or by external signals via death receptors. The latter are only fragmentarily described in invertebrates. In the major invertebrate model organism for studying apoptosis, Caenorhabditis elegans, they have not been described at all. However, in cnidarians TNF-receptors have been identified together with potential ligands and adaptor proteins, such as FADD and TRAF. In Hydra, TNF-R is not coupled with FADD and probably not involved in apoptosis. It rather seems to have a developmental function in specializing epithelial cells in the body column and in tentacles to incorporate nematocytes. With this proposal we want to ask the question of a function for HydraFADDs, if they are not working as adaptors for TNF-R. We want to answer this question by identifying proteins interacting with HyFADD by mass spectrometric analysis. This should explain the molecular context of these proteins in Hydra and serve the understanding of the evolution of extrinsic apoptotic pathways in animals. In addition, by uncovering homologies with vertebrate FADD-interactors we might gain new insights into the role of FADD containing protein complexes, such as death effector filaments for cellular processes in vertebrates, like pathogen defence and inflammation.