Information AboutPerlecan |
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Structure: Perlecan consists of a core protein of molecular weight 450 kDa to which three long chains (each approximately 70-100 kDa) of glycosaminoglycans (often heparan sulfate, HS) are attached. The core protein consists of five distinct structural domains. The N-terminal domain I (aa ~1-195) contains attachment sites for HS chains. Although HS chains are not required for correct folding and secretion of the protein, lack of HS or decreased sulfation can decrease perlecan ability to interact with matrix proteins. Removal of HS chains thus, may affect matrix organization and endothelial barrier function. Domain II comprises four repeats homologous to the ligand-binding portion of the LDL receptor with six conserved cysteine residues and a pentapeptide, DGSDE, which mediates ligand binding by the LDL receptor. Domain III has homology to the domain IVa and IVb of laminin. Domain V, which has homology to the G domain of the long arm of laminin, is responsible for self-assembly and may be important for basement membrane formation in vivo. Thus, perlecan core protein and HS chains could modulate, matrix assembly, cell proliferation, lipoprotein binding and cell adhesion. {Link without Title} {Link without Title} Functions: Perlecan is a key component of vascular extracellualr matrix. It interacts with other matrix components thus help maintain endothelail barrier function. Perlecan is a potent inhibitor of smooth muscle cell proliferation thus thought to maintain vascular homeostais. Perlecan also promote growth factor (e.g. FGF2) activity thus promote endothelail growth and reendothelization. Disease association ''Cartilage development'' - Studies from gene knockout mice and human diseases revealed critical in vivo roles of perlecan in cartilage development and neuromuscular junction activity. ''Cancer'' - While Perlecan suppression caused substantial inhibition of tumor growth and neovascularization in null mice, in contrast, when perlecan-null cells were injected in nude mice they showed enhanced tumor growth as compared to controls ''Diabetes and cardiovascular disease'' Perlecan levels are decreased in many disease states - e.g., diabetes, atherosclerosis and arthritis. Perlecan has an important role in the maintenance of the glomerular filtration barrier. Decreased perlecan in the glomerular basement membrane has a central role in the development of diabetic albuminuria. Perlecan expression is down regulated by many atherogenic stimuli and thus Perlecan is thought to play a protective role in atherosclerosis Selected references Iozzo RV. Perlecan: a gem of a proteoglycan. Matrix Biol. 1994 Apr;14(3):203-8 Pillarisetti S. Lipoprotein modulation of subendothelial heparan sulfate proteoglycans (perlecan) and atherogenicity. Trends Cardiovasc Med. 2000 Feb;10(2):60-5 Hassell J, Yamada Y, Arikawa-Hirasawa E. Role of perlecan in skeletal development and diseases. Glycoconj J. 2002 May-Jun;19(4-5):263-7. Segev A, Nili N, Strauss BH. The role of perlecan in arterial injury and angiogenesis. Cardiovasc Res. 2004 Sep 1;63(4):603-10. Conde-Knape K. Heparan sulfate proteoglycans in experimental models of diabetes: a role for perlecan in diabetes complications. Diabetes Metab Res Rev. 2001 Nov-Dec;17(6):412-21. Gomes RR Jr, Farach-Carson MC, Carson DD. Perlecan functions in chondrogenesis: insights from in vitro and in vivo models. Cells Tissues Organs. 2004;176(1-3):79-86. |
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