The functions of the heparan sulphate proteoglycans.

Abstract

Heparan sulphate (HS)-containing proteoglycans (HS-PGs) are present at the surface of nearly all adherent mammalian cells. The principal mode of attachment is by way of the protein core which is inserted into the plasma membrane. Other forms of HS-PG may be components of pericellular matrices, notably basement membranes. The core proteins of HS-PGs can be small (35K) as in hepatocytes, intermediate (50K) as in many mesenchymal cells, or very large (400K) as in basement membranes. A special case is the HS-PG synthesized by postconfluent fibroblasts. This proteoglycan has a core protein that closely resembles the transferrin receptor glycoprotein. It is possible that this HS-PG is a pro-form of the receptor. Low molecular weight, carbohydrate-rich HS-PG forms are probably derived from larger forms by partial degradation. The HS side-chains can contain 24 different disaccharides in an unknown number of arrangements. The biosynthetic machinery can impose considerable restrictions; for example, the extent of N-sulphation rarely exceeds 40-50%, whereas O-sulphation may range from 20% to 75% of potential sites. Nevertheless, the informational capacity of HS is formidable. By way of the HS chains, HS-PG at the surface of endothelial cells can interact specifically or selectively with a number of plasma proteins. HS-PG at the surface of matrix-producing cells is similarly in a position to interact with matrix proteins, notably collagen, fibronectin and laminin. As the cytoplasmic portion of the HS-PG core protein can bind actin, this proteoglycan can provide a connection between extracellular matrices and the cytoskeleton. A number of studies support a role for HS-PGs in the control of cell growth, and this could be one of their major functions. Whether the HS side-chains or the core protein or both are carrying out such a function remains to be determined.