Why would a change in sulfating of the proteoglycans on the cell surface impact cell behavior?

 

Proteoglycans (PGs) are a family of biomolecules that are composed of a core protein and one or more covalently attached sulfated glycosaminoglycan (GAG) chains. Synthesis and sulfation of GAGs occur on genetically distinct acceptor core proteins within the Golgi, followed by rapid translocation to the cell surface.

Proteoglycans (PGs), composed of a core protein and one or more covalently attached sulfated glycosaminoglycan (GAG) chains, interact with a wide range of bioactive molecules, such as growth factors and chemokines, to regulate cell behaviors in normal and pathological processes. Additionally, PGs, through their compositional diversity, play a broad variety of roles as modulators of proteinase activities. Interactions of proteinases with other molecules on the plasma membrane anchor and activate them at a specific location on the cell surface. These interactions with macromolecules other than their own protein substrates or inhibitors result in changes in their activity and/or may have important biological effects. Thus, GAG chains induce conformational changes upon their binding to peptides or proteins. This behavior may be related to the ability of GAGs to act as modulators for some proteins 1) by acting as crucial structural elements by the control of proteinase activities, 2) by increasing the protein stability, 3) by permitting some binding to occur, exposing binding regions on the target protein, or 4) by acting as co-receptors for some inhibitors, playing important roles for the acceleration of proteinase inhibition. 

The heparan sulfate on the surface of all adherent cells modulates the actions of a large number of extracellular ligands. Members of both cell surface heparan sulfate proteoglycan families, the transmembrane syndecans and the glycosylphosphoinositide-linked glypicans, bind these ligands and enhance formation of their receptor-signaling complexes. These heparan sulfate proteoglycans also immobilize and regulate the turnover of ligands that act at the cell surface. The extracellular domains of these proteoglycans can be shed from the cell surface, generating soluble heparan sulfate proteoglycans that can inhibit interactions at the cell surface. Recent analyses of genetic defects in Drosophila melanogaster, mice, and humans confirm most of these activities in vivo and identify additional processes that involve cell surface heparan sulfate proteoglycans.

Changes in sulfation of proteoglycans thus affect normal functioning of cells.