Chondroitin sulfate and dermatan sulfate

Chondroitin sulfate and dermatan sulfate chains are assembled by the action of a single chondroitin synthase protein featuring two catalytic domains, one catalyzing the b1-4 GalNAc-transferase reaction and the other the b1-3 GlcA-transferase reaction. The only structural difference between chondroitin sulfate and dermatan sulfate is related to the presence of IdoA in the latter. Both types of GAG chains are extensively sulfated by 4-O and 6-O sulfation on GalNAc and 2-O sulfation on GlcA and IdoA. The pattern of sulfation can be determined after digestion with bacterial chondroitinases. These enzymes release the disaccharide GlcA/IdoA(b1-3)GalNAc with different sulfation patterns. The major types of sulfated disaccharides are defined by the letters A to E.

FIG: CHONDROITINASE ACTIVITIES

Most proteoglycans carrying chondroitin sulfate and dermatan sulfate chains are large secreted proteins. These secreted proteoglycans interact with extracellular matrix proteins like collagens and with the large polysaccharide hyaluronan (see the end of this chapter). Another important function of chondroitin sulfate and dermatan sulfate chains is the binding of water molecules, thereby contributing to tissue hydration.

FIG: CS/DS TABLE

The involvement of chondroitin sulfate in tissue hydration is well illustrated by the characterization of the squashed vulva (sqv) mutations in Caenorhabditis elegans. The investigation of worms presenting a collapsed vulva led to the isolation of eight mutated genes, which were designated sqv1 to sqv8. Surprisingly, the identification of the individual sqv genes unraveled the complete pathway of chondroitin polymerization, including the multi-specific UDP-GalNAc/Gal/GlcA transporter (sqv7). Note worthily, neither sulfotransferase, nor proteoglycan genes were found among the sqv mutants. The absence of sulfotransferases probably reflects the fact that chondroitin chains are only poorly sulfated in nematodes. The absence of proteoglycan in the sqv screen is certainly related to the functional redundancy among this class of proteins masking the loss of individual genes.

FIG: SQV MUTATIONS