title: Interaction of extracellular matrix protein 1 with extracellular matrix components: ECM1 is a basement membrane protein of the skin.
abstract: The extracellular matrix protein 1 (ECM1) is a secreted glycoprotein, which plays an important role in the structural and functional biology of the skin as demonstrated by the identification of loss-of-function mutations in ECM1 as cause of the genodermatosis lipoid proteinosis, characterized by reduplication of the skin basement membrane and hyalinization of the underlying dermis. To search for binding partner(s) of ECM1, we tested the in vitro binding activity of ECM1a, a major isoform of four ECM1 splice variants, to different skin extracellular matrix proteins (such as laminin 332, collagen type IV, and fibronectin) and polysaccharides (such as hyaluronan, heparin, and chondroitin sulfate A) with solid-phase binding assay. We demonstrated that ECM1a utilizes different regions to bind to a variety of extracellular matrix components. Ultrastructurally, ECM1 is a basement membrane protein in human skin and is part of network-like suprastructures containing perlecan, collagen type IV, and laminin 332 as constituents. Furthermore, ECM1a enhanced the binding of collagen IV to laminin 332 dose-dependently, showing its involvement in the dermal-epidermal junction and interstitial dermis and making the functional link to the pathophysiology of lipoid proteinosis. To our knowledge, this is previously unreported.
authors.affiliation: Laboratory of Molecular Biotechnology, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Sandy
authors.initials: S
authors.lastname: Sercu
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Noritaka
authors.initials: N
authors.lastname: Oyama
authors.forename: Uwe
authors.initials: U
authors.lastname: Hansen
authors.forename: Abdoel E L
authors.initials: AE
authors.lastname: Ghalbzouri
authors.forename: Gu
authors.initials: G
authors.lastname: Jun
authors.forename: Kristof
authors.initials: K
authors.lastname: Geentjens
authors.forename: Lurong
authors.initials: L
authors.lastname: Zhang
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Merregaert
mesh_terms: D001485:Basement Membrane / Q000378:metabolism*; D001667:Binding, Competitive; D024141:Collagen Type IV / Q000378:metabolism; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D011134:Polysaccharides / Q000737:chemistry; D011485:Protein Binding; D020033:Protein Isoforms; D011994:Recombinant Proteins / Q000737:chemistry; D012867:Skin / Q000378:metabolism*
chemical_list: D024141:Collagen Type IV; C490607:ECM1 protein, human; D016326:Extracellular Matrix Proteins; D011134:Polysaccharides; D020033:Protein Isoforms; D011994:Recombinant Proteins