A current view of perlecan in physiology and pathology: A mosaic of functions

Matrix Biol. 2017 Jan:57-58:285-298. doi: 10.1016/j.matbio.2016.09.003. Epub 2016 Sep 6.

Abstract

Perlecan, a large basement membrane heparan sulfate proteoglycan, is expressed in a wide array of tissues where it regulates diverse cellular processes including bone formation, inflammation, cardiac development, and angiogenesis. Here we provide a contemporary review germane to the biology of perlecan encompassing its genetic regulation as well as an analysis of its modular protein structure as it pertains to function. As perlecan signaling from the extracellular matrix converges on master regulators of autophagy, including AMPK and mTOR, via a specific interaction with vascular endothelial growth factor receptor 2, we specifically focus on the mechanism of action of perlecan in autophagy and angiogenesis and contrast the role of endorepellin, the C-terminal fragment of perlecan, in these cellular and morphogenic events.

Keywords: Angiogenesis; Autophagy; Endorepellin; Heparan sulfate; Proteoglycan.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Autophagy
  • Basement Membrane / cytology
  • Basement Membrane / metabolism*
  • Gene Expression Regulation
  • Heart / growth & development
  • Heparan Sulfate Proteoglycans / genetics*
  • Heparan Sulfate Proteoglycans / metabolism
  • Humans
  • Inflammation
  • Neovascularization, Physiologic / genetics*
  • Organogenesis / genetics*
  • Osteogenesis / genetics
  • Peptide Fragments / genetics*
  • Peptide Fragments / metabolism
  • Protein Domains
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Heparan Sulfate Proteoglycans
  • Peptide Fragments
  • perlecan
  • MTOR protein, human
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases