Biosynthesis of Natural and Hyperelongated Chondroitin Sulfate Glycosaminoglycans: New Insights into an Elusive Process



Peter J. Little*, a, b, c, Mandy L Ballingera, Micah L Burcha, c, Narin Osmana, b
a Diabetes and Cell Biology Laboratory, Vascular and Hypertension Division, BakerIDI Heart and Diabetes Institute,Melbourne, VIC, Australia 3004
b Medicine Departments, Central and Eastern Clinical School,Alfred Hospital, Monash University, Melbourne, VIC, 3004, Australia
c Immunology Departments, Central and Eastern Clinical School,Alfred Hospital, Monash University, Melbourne, VIC, 3004, Australia


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© Little et al. Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Head, Diabetes and Cell Biology Laboratory, BakerIDI, Heart and Diabetes Institute, St. Kilda Rd Central, PO Box 6492, Melbourne, VIC 8008, 75 Commercial Road, Melbourne,VIC 3004, Australia; Tel: +61 3 8532 1203; Fax: +61 3 8532 1100;E-mail: peter.little@bakeridi.edu.au


Abstract

Proteoglycans are important components of the extracellular matrix of all tissues. Proteoglycans are comprised of a core protein and one or more covalently attached glycosaminoglycan (GAG) chains. The major chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans are aggrecan, versican, biglycan and decorin. Cells synthesize GAGs of natural or basal lengths and the GAG chains are subject to considerable growth factor, hormonal and metabolic regulation to yield longer GAG chains with altered structure and function. The mechanism by which the CS/DS GAG chains are polymerized is unknown. Recent work has identified several monosaccharide transferases which when co-expressed yield GAG polymers and the length of the polymers depends upon the pair of enzymes coexpressed. The further extension of these chains is regulated by signaling pathways. Inhibition of these latter pathways may be a therapeutic target to prevent the elongation which is associated with increased binding of atherogenic lipids and the disease process of atherosclerosis.

Keywords: Proteoglycans, chondroitin sulfate, glycosaminoglycans, enzymology, polymerases, signaling.