title: SLURP1 is a late marker of epidermal differentiation and is absent in Mal de Meleda.
abstract: SLURP1 is a secreted member of the LY6/PLAUR protein family. Mutations in the SLURP1 gene are the cause of Mal de Meleda (MDM), a rare autosomal recessive genetic disease, characterized by inflammatory palmoplantar keratoderma. In this study, we have analyzed the expression of SLURP1 in normal and MDM skin. SLURP1 was found to be a marker of late differentiation, predominantly expressed in the granular layer of skin, notably the acrosyringium. Moreover, SLURP1 was also identified in several biological fluids such as sweat, saliva, tears, and urine from normal volunteers. In palmoplantar sections from MDM patients, as well as in their sweat, mutant SLURP1, including the new variant R71H-SLURP1, was either absent or barely detectable. Transfected human embryonic kidney 293T cells expressed the MDM mutant SLURP1 containing the single amino-acid substitution G86R but did not tolerate the MDM mutation W15R located in the signal peptide. Thus, most MDM mutations in SLURP1 affect either the expression, integrity, or stability of the protein, suggesting that a simple immunologic test could be used as a rapid screening procedure.
authors.affiliation: Laboratory of Cutaneous Biology, Department of Dermatology, CHUV, Lausanne, Switzerland.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Favre
authors.forename: Laure
authors.initials: L
authors.lastname: Plantard
authors.forename: Lorène
authors.initials: L
authors.lastname: Aeschbach
authors.forename: Noureddine
authors.initials: N
authors.lastname: Brakch
authors.forename: Stephanie
authors.initials: S
authors.lastname: Christen-Zaech
authors.forename: Pierre A
authors.initials: PA
authors.lastname: de Viragh
authors.forename: Ann
authors.initials: A
authors.lastname: Sergeant
authors.forename: Marcel
authors.initials: M
authors.lastname: Huber
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
mesh_terms: D000950:Antigens, Ly / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004817:Epidermis / Q000473:pathology*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D012867:Skin / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D015415:Biomarkers; C048963:SLURP1 protein, human; D014568:Urokinase-Type Plasminogen Activator; D002118:Calcium