Background information
The tumor necrosis factor receptor (TNFR) superfamily represents a growing family of type I transmembrane glycoproteins that are involved in various cellular functions, including proliferation, differentiation and programmed cell death. These proteins share homology for cysteine-rich repeats in the extracellular ligand binding domain and an intracellular death domain. Members of the TNFR superfamily transmit signals through protein-protein interactions, and these signals can lead to the activation of either the caspase and Jun kinase pathways, which promote cell death, or the NFκB pathway, which results in cell survival. The ectodermal dysplasia receptor (EDAR) promotes all three of these pathways and mediates ectodermal differentiation. EDAR is encoded by the downless gene and is mutated in ectodermal dysplasia syndromes, which are characterized by impaired hair, teeth and sweat gland development. Ectodysplasin A (EDA) is a type II membrane protein that is encoded by the Tabby gene and produces many splice variants, the longest of which, EDA-A1, serves as the ligand for EDAR. EDA-A2, which differs from EDA-A1 by the deletion of two amino acids, binds only the X-linked ectodysplasin-A2 receptor (XEDAR). Both EDAR and XEDAR exhibit homology with TROY.
