Fibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing.

TitleFibronectin matrix as a scaffold for procollagen proteinase binding and collagen processing.
Publication TypeJournal Article
Year of Publication2019
AuthorsSaunders, JT, Schwarzbauer, JE
JournalMol Biol Cell
Date Published2019 Aug 01
KeywordsBinding Sites, Bone Morphogenetic Protein 1, Collagen, Extracellular Matrix, Extracellular Matrix Proteins, Fibroblasts, Fibronectins, Humans, Primary Cell Culture, Procollagen, Protein Binding, Proteolysis

<p>The extracellular matrix (ECM) proteins fibronectin (FN) and type I collagen (collagen I) are codistributed in many tissues, and collagens have been shown to depend on an FN matrix for fibrillogenesis. Microscopic analysis of a fibroblast ECM showed colocalization of procollagen I with FN fibrils, and proteolytic cleavage of procollagen to initiate fibril formation was significantly reduced with inhibition of FN matrix assembly. We examined the role of FN matrix in procollagen processing by the C-propeptide proteinase bone morphogenetic protein 1 (BMP-1). We found that BMP-1 binds to a cell-assembled ECM in a dose-dependent manner and that, like procollagen, BMP-1 colocalizes with FN fibrils in the matrix microenvironment. Binding studies with FN fragments identified a binding site in FN's primary heparin-binding domain. In solution, BMP-1-FN interactions and BMP-1 cleavage of procollagen I were both enhanced by the presence of heparin, suggesting a role for heparin in complex formation during proteolysis. Indeed, addition of heparin enhanced the rate of procollagen cleavage by matrix-bound BMP-1. Our results show that matrix localization of this proteinase facilitates the initiation of collagen assembly and suggest a model in which FN matrix and associated heparan sulfate act as a scaffold to organize enzyme and substrate for procollagen processing.</p>

Alternate JournalMol Biol Cell
PubMed ID31242089
PubMed Central IDPMC6743462
Grant ListR01 AR073236 / AR / NIAMS NIH HHS / United States
R01 CA160611 / CA / NCI NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States