Fulltext

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

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

In: Human Molecular Genetics, 2003, vol. 12, no. 22, p. 3017-3024

Add to personal list
    Title
    • Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda
    Author
    • Chimienti, Fabrice. Laboratory for Cutaneous Biology, Dermatology Unit, CHUV, Lausanne, Switzerland
    • Hogg, Ronald C.. Department of Physiology, CMU, Geneva, Switzerland
    • Plantard, Laure. Laboratory for Cutaneous Biology, Dermatology Unit, CHUV, Lausanne, Switzerland
    • Lehmann, Caroline. Laboratory for Cutaneous Biology, Dermatology Unit, CHUV, Lausanne, Switzerland
    • Brakch, Noureddine. Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland and
    • Fischer, Judith. Centre National de Génotypage, Evry, France
    • Huber, Marcel. Laboratory for Cutaneous Biology, Dermatology Unit, CHUV, Lausanne, Switzerland
    • Bertrand, Daniel. Department of Physiology, CMU, Geneva, Switzerland
    • Hohl, Daniel. Laboratory for Cutaneous Biology, Dermatology Unit, CHUV, Lausanne, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Human Molecular Genetics, 2003, vol. 12, no. 22, p. 3017-3024. Oxford University Press
    Other Version
    Classification
    • Health
    OAI-PMH Identifier
    • oai:doc.rero.ch:298352
    Summary
    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