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Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda
Open accessAbstract
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.
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“For example, SLURP-1 is mutated in Mal de Meleda (120).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [120]
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Metadata
- Authors
- Chimienti, F.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Chimienti, F.
- ORCID
- Chimienti, F.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-09-18
- Volume
- 12
- Issue
- 22
- Pages
- 3017-3024
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2127747996
- Cited by
- 247
- References
- 40
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 2 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 11 · 2016: 14 · 2015: 16 · 2014: 12 · 2013: 9 · 2012: 18
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- IRIS (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Health Sciences › Medicine › Dermatology › Genetic and rare skin diseases.
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- SLURP-1, Mal de Meleda, alpha7 nicotinic acetylcholine receptor, keratinocytes, keratosis, anti-TNF therapy, macrophages, wound healing, epidermal homeostasis, autosomal recessive inheritance
- MeSH terms
- Acetylcholine, Amino Acid Sequence, Animals, Antigens, Ly, Cell Line, Cell Nucleus, Clone Cells, Dose-Response Relationship, Drug, Epidermis, Female, Genes, Recessive, Humans, Keratoderma, Palmoplantar, Microinjections, Models, Molecular, Moths, Mutation, Oocytes, Peptides, Phenotype, Receptors, Cholinergic, Recombinant Proteins, Urokinase-Type Plasminogen Activator, Xenopus laevis, Protein Structure, Tertiary, DNA, Complementary, Neurotransmitter Agents, Patch-Clamp Techniques
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