Molecular Mechanisms of apoptosis in Hydra

水螅细胞凋亡的分子机制

• 批准号: 217550288
• 负责人: Professorin Dr. Angelika Böttger
• 金额: --
• 依托单位: Abteilung für Zell- und Entwicklungsbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/217550288?language=en
• 关键词: Molecular; Mechanisms; apoptosis; Hydra

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.

细胞凋亡是一种动物特异性的程序性细胞死亡，其由Bcl-2家族成员和半胱天冬酶调节。这些分子通路在所有动物中是保守的，甚至在前两侧动物中也是如此，例如刺胞动物水螅，我们可以鉴定出广泛的凋亡蛋白网络。细胞凋亡可以从细胞内诱导，例如通过DNA损伤或通过经由死亡受体的外部信号。后者仅在无脊椎动物中有零星描述。在研究细胞凋亡的主要无脊椎动物模式生物秀丽隐杆线虫中，它们根本没有被描述过。然而，在刺胞动物中，TNF-受体已与潜在的配体和衔接蛋白（如FADD和TRAF）一起被鉴定。在水螅中，TNF-R不与FADD偶联，可能不参与细胞凋亡。相反，它似乎有一种发育功能，使体柱和触须中的上皮细胞特化，以整合巨噬细胞。通过该提案，我们想询问HydraFADD的功能问题，如果它们不作为TNF-R的适配器。我们想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。这应该解释这些蛋白质在水螅的分子背景，并服务于理解在动物中的外在凋亡途径的演变。此外，通过揭示与脊椎动物FADD相互作用的同源性，我们可能会获得新的见解FADD含有蛋白质复合物的作用，如死亡效应丝在脊椎动物中的细胞过程，如病原体防御和炎症。