title: The NTR domain of procollagen C-proteinase enhancer-1 (PCPE-1) mediates PCPE-1 binding to syndecans-1, -2 and -4 as well as fibronectin.
abstract: Procollagen C-proteinase enhancer 1 (PCPE-1) is an extracellular matrix glycoprotein that can stimulate procollagen processing by procollagen C-proteinases (PCPs) such as bone morphogenetic protein-1 (BMP-1). PCPE-1 consists of two CUB domains that bind to the procollagen C-propeptide and are responsible for enhancing activity and a netrin-like (NTR) domain that binds to BMP-1 as well as heparin and heparan sulfate. The NTR domain also mediates binding of PCPE-1 to cells, an interaction inhibited by heparin, thus suggesting involvement of cell membrane heparan-sulfate proteoglycans (HSPGs). Using pull-down experiments and an ELISA type binding assay we show here that PCPE-1 binds to three cell membrane HSPGs, syndecans-1, -2 and -4. We also demonstrate that this binding is mediated by the NTR domain and depends on the glycosaminoglycan chains of the syndecans. Using co-immunoprecipitation and an ELISA type binding assay we show that PCPE-1 can also bind fibronectin (an established binding partner of BMP-1), another interaction involving the NTR domain. Consistently, fibronectin inhibits cell attachment to PCPE-1 although it does not affect PCPE-1 enhancing activity. PCPE-1 is not an adhesive protein since cell attachment to PCPE-1 is not associated with cell spreading and/or actin filaments formation. The results suggest that PCPE-1 binding to syndecans and/or fibronectin may control collagen fibril assembly on the cell surface. Further characterization of these interactions may pave the way for future design of new means to modulate collagen deposition in pathological conditions such as fibrosis.
authors.affiliation: Maurice and Gabriela Goldschleger Eye Research Institute, Tel Aviv University Sackler Faculty of Medicine, Sheba Medical Center, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Weiss
authors.affiliation: Maurice and Gabriela Goldschleger Eye Research Institute, Tel Aviv University Sackler Faculty of Medicine, Sheba Medical Center, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Brusel
authors.affiliation: Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR 5305, CNRS, Université Lyon 1, SFR BioSciences Gerland-Lyon Sud, Lyon, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rousselle
authors.affiliation: Maurice and Gabriela Goldschleger Eye Research Institute, Tel Aviv University Sackler Faculty of Medicine, Sheba Medical Center, Israel. Electronic address: ekessler@post.tau.ac.il.
authors.forename: Efrat
authors.initials: E
authors.lastname: Kessler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D053667:Syndecans / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D006023:Glycoproteins; C491555:PCOLCE protein, human; D053667:Syndecans
keywords: Fibronectin; Heparin binding; Procollagen C-proteinase enhancer-1; Procollagen processing; Syndecans