The leucine-rich repeat protein PRELP binds fibroblast cell surface proteoglycans and enhances focal adhesion formation.

PRELP is a member of the leucine-rich repeat family of extracellular matrix proteins in connective tissue. In contrast to other members of the family, the amino-terminal domain of PRELP has a high content of proline and positively charged amino acids. This domain has previously been shown to bind chondrocytes and to inhibit osteoclast differentiation. Here we show that PRELP mediates cell adhesion by binding to cell surface glycosaminoglycans. Thus, rat skin fibroblasts bound to full-length PRELP and to the amino-terminal part of PRELP alone, but not to truncated PRELP lacking the positively charged amino-terminal region. Cell attachment to PRELP was inhibited by addition of soluble heparin or heparan sulfate, by blocking sulfation of the fibroblasts, or by treating the cells with a combination of chondroitinase and heparinase. Using affinity chromatography, we identified syndecan-1, syndecan-4 and glypican-1 as cell surface proteoglycans binding to the amino-terminal part of PRELP. Finally, we show that the amino-terminal domain of PRELP in combination with the integrin-binding domain of fibronectin, but neither of the fragments alone, induced fibroblast focal adhesion formation. These findings provide support for a role of the amino-terminal region of PRELP as an important regulator of cell adhesion and behavior, which may be of importance in pathological conditions.