Characterization of C. elegans Chondroitin Proteoglycans and Their Large Functional and Structural Heterogeneity; Evolutionary Aspects on Structural Differences Between Humans and the Nematode.

Proteoglycans regulate important cellular pathways in essentially all metazoan organisms. While considerable effort has been devoted to study structural and functional aspects of proteoglycans in vertebrates, the knowledge of the core proteins and proteoglycan-related functions in invertebrates is relatively scarce, even for C.elegans. This nematode produces a large amount of non-sulfated chondroitin in addition to small amount of low-sulfated chondroitin chains (Chn and CS chains, respectively). Until recently, 9 chondroitin core proteins (CPGs) had been identified in C.elegans, none of which showed any homology to vertebrate counterparts or to other invertebrate core proteins. By using a glycoproteomic approach, we recently characterized the chondroitin glycoproteome of C.elegans, resulting in the identification of 15 novel CPG core proteins in addition to the 9 previously established. Three of the novel core proteins displayed homology to human proteins, indicating that CPG and CSPG core proteins may be more conserved throughout evolution than previously perceived. Bioinformatic analysis of the primary amino acid sequences revealed that the core proteins contained a broad range of functional domains, indicating that specialization of proteoglycan-mediated functions may have evolved early in metazoan evolution. This review specifically discusses our recent data in relation to previous knowledge of core proteins and GAG-attachment sites in Chn and CS proteoglycans of C.elegans and humans, and point out both converging and diverging aspects of proteoglycan evolution.