The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement membrane anchor

J Biol Chem. 2002 Apr 26;277(17):15061-8. doi: 10.1074/jbc.M108285200. Epub 2002 Feb 14.

Abstract

PRELP (proline arginine-rich end leucine-rich repeat protein) is a heparin-binding leucine-rich repeat protein in connective tissue extracellular matrix. In search of natural ligands and biological functions of this molecule, we found that PRELP binds the basement membrane heparan sulfate proteoglycan perlecan. Also, recombinant perlecan domains I and V carrying heparan sulfate bound PRELP, whereas other domains without glycosaminoglycan substitution did not. Heparin, but not chondroitin sulfate, inhibited the interactions. Glycosaminoglycan-free recombinant perlecan domain V and mutated domain I did not bind PRELP. The dissociation constants of the PRELP-perlecan interactions were in the range of 3-18 nm as determined by surface plasmon resonance. As expected, truncated PRELP, without the heparin-binding domain, did not bind perlecan. Confocal immunohistochemistry showed that PRELP outlines basement membranes with a location adjacent to perlecan. We also found that PRELP binds collagen type I and type II through its leucine-rich repeat domain. Electron microscopy visualized a complex with PRELP binding simultaneously to the triple helical region of procollagen I and the heparan sulfate chains of perlecan. Based on the location of PRELP and its interaction with perlecan heparan sulfate chains and collagen, we propose a function of PRELP as a molecule anchoring basement membranes to the underlying connective tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Collagen / metabolism*
  • Extracellular Matrix Proteins / metabolism*
  • Glycoproteins / metabolism*
  • Heparan Sulfate Proteoglycans / metabolism*
  • Mice
  • Protein Binding

Substances

  • Extracellular Matrix Proteins
  • Glycoproteins
  • Heparan Sulfate Proteoglycans
  • Prelp protein, mouse
  • perlecan
  • Collagen