The evolutionary origins of the tumor necrosis factor receptor family - cell death or differentiation?

Abstract

TNF-R, TNF, and FADD family members are conserved in the fresh water polyp Hydra. Moreover, Hydra expresses HyTNF-R adaptor proteins similar to the vertebrate TNF-receptor associated factors TRAF-4 and TRAF-6. HyTNF-R is closest related to the human ectodysplasin receptor EDAR, which is involved in epithelial cell differentiation, e.g. the formation of hair and tooth cells in mammals. Consistent with a similar function in Hydra, we show here that HyTNF-R protein is localised very specifically in battery cells and in such epithelial cells of the body column that incorporate nematocytes. Epithelial cell differentiation is therefore an evolutionary ancient function of TNF-R/TNF-protein superfamily members. We also show that two Hydra-FADD proteins co-localise with Hydra caspases possessing death (DD) or death effector (DED) domains in death effector filaments in human cells. Caspase recruitment by members of the FADD-protein family might therefore also be an ancient trait. Future research will have to discover the up-stream pathways, which govern this potential apoptotic pathway in Hydra and whether it is extrinsically or intrinsically induced.