Biodiversity of CS–proteoglycan sulphation motifs: chemical messenger recognition modules with roles in information transfer, control of cellular behaviour and tissue morphogenesis

Chondroitin sulphate glycosaminoglycan chains on cell and ECM proteoglycans can no longer be regarded as merely hydrodynamic space fillers. Overwhelming evidence over recent years indicates that sulphation motif sequences within the chondroitin sulphate chain structure are a source of significant biological information to cells and their surrounding environment. Chondroitin sulphate sulphation motifs have been shown to interact with a wide variety of bioactive molecules e.g. cytokines, growth factors, chemokines, morphogenetic proteins, enzymes and enzyme inhibitors, as well as structural components within the extracellular milieu. They are therefore capable of modulating a panoply of signalling pathways thus controlling diverse cellular behaviours including proliferation, differentiation, migration and matrix synthesis. Consequently, through these motifs, chondroitin sulphate proteoglycans play significant roles in the maintenance of tissue homeostasis, morphogenesis, development, growth and disease. Here we review (i) the biodiversity of chondroitin sulphate proteoglycans and their sulphation motif sequences and (ii) the current understanding of the signalling roles they play in regulating cellular behaviour during tissue development, growth, disease and repair