Molecular Mechanisms of apoptosis in Hydra

细胞凋亡是一种动物特有的程序性细胞死亡，由Bcl2家族成员和半胱氨酸天冬氨酸酶调节。这些分子通路在所有动物中都是保守的，甚至在双侧前动物中也是如此，比如刺蛇，我们可以确定一个广泛的凋亡蛋白网络。细胞凋亡可以从细胞内部诱导，例如通过DNA损伤或通过死亡受体的外部信号。后者在无脊椎动物中只有零星的描述。在研究细胞凋亡的主要无脊椎动物模式生物秀丽线虫中，它们根本就没有被描述过。然而，在线虫中，已发现肿瘤坏死因子受体与潜在的配体和适配器蛋白一起被发现，如FADD和TRAF。在九头蛇中，肿瘤坏死因子受体不与FADD偶联，可能不参与细胞凋亡。相反，它似乎具有发育功能，使体柱和触须中的上皮细胞专门化，以结合线虫细胞。在这项提议中，我们想问一个问题，如果HydraFADD不能作为肿瘤坏死因子受体的接头，它们的功能是什么？我们希望通过质谱分析鉴定与HyFADD相互作用的蛋白质来回答这个问题。这应该可以解释这些蛋白质在九头蛇中的分子背景，并有助于理解动物体内外在细胞凋亡途径的进化。此外，通过揭示与脊椎动物FADD相互作用蛋白的同源性，我们可能对含有FADD的蛋白质复合体的作用有新的见解，例如脊椎动物细胞过程中的死亡效应细丝，如病原体防御和炎症。

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.