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

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  • Fabrice Chimienti
  • Ronald C Hogg
  • Laure Plantard
  • Caroline Lehmann
  • Noureddine Brakch
  • Judith Fischer
  • Marcel Huber
  • Daniel Bertrand
  • Daniel Hohl
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.
OriginalsprogEngelsk
TidsskriftHuman Molecular Genetics
Vol/bind12
Udgave nummer22
Sider (fra-til)3017-24
Antal sider8
ISSN0964-6906
DOI
StatusUdgivet - 15 nov. 2003

ID: 45161578