Abstract
Members of the tumor necrosis factor (TNF) family, best known for their roles in immunity and inflammation, are now shown to function in the morphogenesis of hair follicles in the epidermis. Yan et al . report the identification of two TNF receptor family members as binding partners for two products of the EDA gene. Mutations in this gene cause the disorder anhidrotic ectodermal dysplasia (EDA) in which patients lose hair, sweat glands, and teeth. The EDA gene produces two membrane-bound proteins with TNF-like domains that differ by an insert of only two amino acids. This small difference, however, is enough to cause essentially all-or-none binding to their respective receptors. EDA-A1, the longer isoform, binds exclusively to the receptor called EDAR, whereas the shorter, EDA-A2, binds exclusively to the related receptor called XEDAR (for X-linked ectodysplasin-A2 receptor). The two receptor-morphogen pairs appear to have distinct functions in the development of hair follicles. Yan, M., Wang, L.-C., Hymowitz, S.G., Schilbach, S., Lee, J., Goddard, A., de Vos, A.M., Gao, W.-Q., and Dixit, V.M. (2000) Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors. Science 290 : 523-527. [Abstract] [Full Text]
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