Cellular functions of proteoglycans--an overview.

This issue of Seminars in Cell and Developmental Biology contains a number of articles reviewing the cellular functions of proteoglycans. Proteoglycans are proteins, substituted with glycosaminoglycans (GAGs), that generally either decorate the cell membrane or fill the extracellular space. GAGs are linear polysaccharides consisting of a repeating disaccharide, generally of an acetylated amino sugar alternating with a uronic acid. Although there are intracellular types, most proteoglycans are destined for the extracellular space. These are very diverse molecules, and various combinations of both different types of proteins [matrix, cell surface transmembrane or covalently linked to membrane glycosylphosphatidylinositol (GPI)] and classes of GAG chains [hyaluronan (HA), chondroitin sulfate (CS), keratan sulfate (KS), dermatan sulfate (DS) and heparan sulfate (HS)] are found in vertebrates. For example, the syndecan transmembrane proteins can be decorated with two HS and one CS chains, while the aggrecan cartilage matrix protein is typically decorated by about 100 CS and 30 KS chains, and decorin, a major proteoglycan of the interstitial matrix, contains a single DS chain. Further, GAGs may decorate only a proportion of a type of protein. The function of the GAG substituent in these so-called ‘part-time proteoglycans’ is rarely understood. Proteoglycans can be very abundant. At the surface of epithelial cells, it has been estimated that there may be as many as 1 million syndecan-1 molecules, and cartilage matrix is a several mg per ml composite of aggrecan with HA. HA, the structurally most simple GAG, is not an authentic proteoglycan, as it is not co-