Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Mal de Meleda is an autosomal recessive inflammatory and keratotic palmoplantar skin disorder due to mutations in the ARS B gene, encoding for SLURP-1 (secreted mammalian Ly-6/uPAR-related protein 1). SLURP-1 belongs to the Ly-6/uPAR superfamily of receptor and secreted proteins, which participate in signal transduction, immune cell activation or cellular adhesion. The high degree of structural similarity between SLURP-1 and the three fingers motif of snake neurotoxins and Lynx1 suggests that this protein interacts with the neuronal acetylcholine receptors. We found that SLURP-1 potentiates the human alpha 7 nicotinic acetylcholine receptors that are present in keratinocytes. These results identify SLURP-1 as a secreted epidermal neuromodulator which is likely to be essential for both epidermal homeostasis and inhibition of TNF-alpha release by macrophages during wound healing. This explains both the hyperproliferative as well as the inflammatory clinical phenotype of Mal de Meleda.
Originalsprog | Engelsk |
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Tidsskrift | Human Molecular Genetics |
Vol/bind | 12 |
Udgave nummer | 22 |
Sider (fra-til) | 3017-24 |
Antal sider | 8 |
ISSN | 0964-6906 |
DOI | |
Status | Udgivet - 15 nov. 2003 |
ID: 45161578