Abstract / Description of output
Members of the tumour-necrosis factor receptor (TNFR) family that contain an intracellular death domain initiate signalling by recruiting cytoplasmic death domain adapter proteins. Edar is a death domain protein of the TNFR family that is required for the development of hair, teeth and other ectodermal derivatives. Mutations in Edar-or its ligand, Eda-cause hypohidrotic ectodermal dysplasia in humans and mice. This disorder is characterized by sparse hair, a lack of sweat glands and malformation of teeth. Here we report the identification of a death domain adapter encoded by the mouse crinkled locus. The crinkled mutant has an hypohidrotic ectodermal dysplasia phenotype identical to that of the edar (downless) and eda (Tabby) mutants. This adapter, which we have called Edaradd (for Edar-associated death domain), interacts with the death domain of Edar and links the receptor to downstream signalling pathways. We also identify a missense mutation in its human orthologue, EDARADD, that is present in a family affected with hypohidrotic ectodermal dysplasia. Our findings show that the death receptor/adapter signalling mechanism is conserved in developmental, as well as apoptotic, signalling.
Original language | English |
---|---|
Pages (from-to) | 913-6 |
Number of pages | 4 |
Journal | Nature |
Volume | 414 |
Issue number | 6866 |
DOIs | |
Publication status | Published - 2001 |
Keywords / Materials (for Non-textual outputs)
- Amino Acid Sequence
- Animals
- Cell Line
- Ectodermal Dysplasia
- Edar Receptor
- Gene Expression
- Humans
- Membrane Proteins
- Mice
- Mice, Inbred C3H
- Mice, Inbred C57BL
- Molecular Sequence Data
- Mutation
- NF-kappa B
- Protein Binding
- Protein Structure, Tertiary
- Receptors, Ectodysplasin
- Receptors, Tumor Necrosis Factor
- Sequence Homology, Amino Acid
- Signal Transduction