For EDAR and EDARADD autosomal mutations, it is interesting to note that dominant mutations are mainly localized in the interaction domain, resulting in impaired oligomerization and a dominant negative effect. (A) Principal model for the EDA pathway downstream signaling: the trimeric ligand EDA binds to the trimeric receptor EDAR leading to the recruitment of the adaptor EDARADD and the formation of a complex containing EDARADD, TRAF6, TAB2, and TAK1. TAK1 activates the IKK complex (IKK1, IKK2, and NEMO) which ubiquitinates I-kappa-B, leading to the release of NF-kappa-B transcription factor. NF-kappa-B is then translocated into the nucleus to activate target genes. (B) EDA, EDAR, and EDARADD proteins and their functional domains. Principal mutations are indicated.
Reproduced from: Sadier A, Viriot L, Pantalacci S, Laudet V. The ectodysplasin pathway: from diseases to adaptations. Trends Genet 2014; 30:24. Illustration used with the permission of Elsevier Inc. All rights reserved.