Biosynthesis and regulation of expression of proteoglycans

Proteoglycans are a family of complex macromolecules characterized by the presence of one or more glycosaminoglycan chains covalently linked to a polypeptide backbone. Although originally named and categorized on the basis of the glycosaminoglycan substituent, increasingly they are being identified as members of gene families that encode their different core proteins. Proteoglycans are found predominantly in the extracellular matrix (ECM) or associated with the cell surface of most eucaryotic cells where they bind to other matrix- and cell-associated components. Their ability to be so interactive stems in large part from their structural diversity, which arises from variations in polysaccharide type, size and composition as well as core protein primary sequence, domain arrangement, degree of substitution and distribution of polysaccharide chains. Considering the complexity of proteoglycan molecules, often having modular core protein domains and posttranslational modifications that vary with developmental setting, the various steps of synthesis and processing are most likely highly regulated. Furthermore, regulation of proteoglycan expression is even more complex as they frequently are expressed transiently by multiple cell types and in different developmental time frames. Elucidation of cell- and developmental-specific control elements which regulate the expression of these complex macromolecular families are only beginning.