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

Tali Weiss, Marina Brusel, Patricia Rousselle, Efrat Kessler

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)45-53
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume57
DOIs
StatePublished - Dec 2014

Keywords

  • Fibronectin
  • Heparin binding
  • Procollagen C-proteinase enhancer-1
  • Procollagen processing
  • Syndecans

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