Expanding the Chondroitin Glycoproteome of Caenorhabditis elegans

J Biol Chem. 2018 Jan 5;293(1):379-389. doi: 10.1074/jbc.M117.807800. Epub 2017 Nov 14.


Chondroitin sulfate proteoglycans (CSPGs) are important structural components of connective tissues in essentially all metazoan organisms. In vertebrates, CSPGs are involved also in more specialized processes such as neurogenesis and growth factor signaling. In invertebrates, however, knowledge of CSPGs core proteins and proteoglycan-related functions is relatively limited, even for Caenorhabditis elegans. This nematode produces large amounts of non-sulfated chondroitin in addition to low-sulfated chondroitin sulfate chains. So far, only nine core proteins (CPGs) have been identified, some of which have been shown to be involved in extracellular matrix formation. We recently introduced a protocol to characterize proteoglycan core proteins by identifying CS-glycopeptides with a combination of biochemical enrichment, enzymatic digestion, and nano-scale liquid chromatography MS/MS analysis. Here, we have used this protocol to map the chondroitin glycoproteome in C. elegans, resulting in the identification of 15 novel CPG proteins in addition to the nine previously established. Three of the newly identified CPGs displayed homology to vertebrate proteins. Bioinformatics analysis of the primary protein sequences revealed that the CPG proteins altogether contained 19 unique functional domains, including Kunitz and endostatin domains, suggesting direct involvement in protease inhibition and axonal migration, respectively. The analysis of the core protein domain organization revealed that all chondroitin attachment sites are located in unstructured regions. Our results suggest that CPGs display a much greater functional and structural heterogeneity than previously appreciated and indicate that specialized proteoglycan-mediated functions evolved early in metazoan evolution.

Keywords: Caenorhabditis elegans (C. elegans); chondroitin; glycosaminoglycan; mass spectrometry (MS); proteoglycan; proteoglycan structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chondroitin Sulfate Proteoglycans / chemistry*
  • Chondroitin Sulfate Proteoglycans / isolation & purification
  • Chondroitin Sulfate Proteoglycans / metabolism*
  • Chondroitin Sulfates / metabolism
  • Chromatography, Gel / methods
  • Glycopeptides / metabolism
  • Proteoglycans / metabolism
  • Tandem Mass Spectrometry / methods


  • Caenorhabditis elegans Proteins
  • Chondroitin Sulfate Proteoglycans
  • Glycopeptides
  • Proteoglycans
  • Chondroitin Sulfates