A current view of perlecan in physiology and pathology: A mosaic of functions.
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.
Department of Pathology, Anatomy, and Cell Biology and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States.
Maria A
MA
Gubbiotti
Department of Pathology, Anatomy, and Cell Biology and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States.
Thomas
T
Neill
Department of Pathology, Anatomy, and Cell Biology and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States. Electronic address: renato.iozzo@jefferson.edu.
Renato V
RV
Iozzo
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D001485:Basement Membrane / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006321:Heart / Q000254:growth & development; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D018919:Neovascularization, Physiologic / Q000235:genetics*; D038081:Organogenesis / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D000072417:Protein Domains; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D019812:Heparan Sulfate Proteoglycans; D010446:Peptide Fragments; C071927:perlecan; C546842:MTOR protein, human; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
Angiogenesis; Autophagy; Endorepellin; Heparan sulfate; Proteoglycan