Journal Article

Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda

Fabrice Chimienti, Ronald C. Hogg, Laure Plantard, Caroline Lehmann, Noureddine Brakch, Judith Fischer, Marcel Huber, Daniel Bertrand and Daniel Hohl

in Human Molecular Genetics

Volume 12, issue 22, pages 3017-3024
Published in print November 2003 | ISSN: 0964-6906
Published online November 2003 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg320
Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda

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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 α7 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.

Journal Article.  4435 words.  Illustrated.

Subjects: Genetics and Genomics

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