title: Ectodysplasin is a collagenous trimeric type II membrane protein with a tumor necrosis factor-like domain and co-localizes with cytoskeletal structures at lateral and apical surfaces of cells.
abstract: Anhidrotic ectodermal dysplasia (EDA) is a human genetic disorder of impaired ectodermal appendage development. The EDA gene encodes isoforms of a novel transmembrane protein, ectodysplasin. The sequence of the longest isoform includes an interrupted collagenous domain of 19 Gly-X-Y repeats and a motif conserved in the tumor necrosis factor (TNF)-related ligand family. In order to understand better the function of the ectodysplasin protein molecule and its domains, we have studied the processing and localization of wild-type and mutated isoforms in transfected human fetal kidney 293 and monkey kidney COS-1 cells. Similar to other members of collagenous membrane proteins and members of TNF-related ligands, ectodysplasin is a type II membrane protein and it forms trimers. The membrane localization of ectodysplasin is asymmetrical: it is found on the apical and lateral surfaces of the cells where it co-localizes with cytoskeletal structures. The TNF-like motif and cysteines found near the C-terminus are necessary for correct transport to the cell membrane, but the intracellular and collagenous domains are not required for the localization pattern. Our results suggest that ectodysplasin is a new member in the TNF-related ligand family involved in the early epithelial-mesenchymal interaction that regulates ectodermal appendage formation.
authors.affiliation: Department of Medical Genetics, Haartman Institute, National Institute of Aging, Baltimore, MD 21224, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ezer
authors.forename: M
authors.initials: M
authors.lastname: Bayés
authors.forename: O
authors.initials: O
authors.lastname: Elomaa
authors.forename: D
authors.initials: D
authors.lastname: Schlessinger
authors.forename: J
authors.initials: J
authors.lastname: Kere
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016764:Cell Polarity; D003094:Collagen / Q000737:chemistry; D003599:Cytoskeleton / Q000737:chemistry*; D004476:Ectodermal Dysplasia / Q000235:genetics*; D053331:Ectodysplasins; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000737:chemistry; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C506018:EDA protein, human; D053331:Ectodysplasins; D008024:Ligands; D008565:Membrane Proteins; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen