Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
---|---|
Journal | Human Molecular Genetics |
Volume | 12 |
Issue number | 22 |
Pages (from-to) | 3017-24 |
Number of pages | 8 |
ISSN | 0964-6906 |
DOIs | |
Publication status | Published - 15 Nov 2003 |
- Acetylcholine, Amino Acid Sequence, Animals, Antigens, Ly, Cell Line, Cell Nucleus, Clone Cells, DNA, Complementary, Dose-Response Relationship, Drug, Epidermis, Female, Genes, Recessive, Humans, Keratoderma, Palmoplantar, Microinjections, Models, Molecular, Moths, Mutation, Neurotransmitter Agents, Oocytes, Patch-Clamp Techniques, Peptides, Phenotype, Protein Structure, Tertiary, Receptors, Cholinergic, Recombinant Proteins, Urokinase-Type Plasminogen Activator, Xenopus laevis
Research areas
ID: 45161578