title: Nematodes join the family of chondroitin sulfate-synthesizing organisms: Identification of an active chondroitin sulfotransferase in Caenorhabditis elegans.
abstract: Proteoglycans are proteins that carry sulfated glycosaminoglycans (GAGs). They help form and maintain morphogen gradients, guiding cell migration and differentiation during animal development. While no sulfated GAGs have been found in marine sponges, chondroitin sulfate (CS) and heparan sulfate (HS) have been identified in Cnidarians, Lophotrocozoans and Ecdysozoans. The general view that nematodes such as Caenorhabditis elegans, which belong to Ecdysozoa, produce HS but only chondroitin without sulfation has therefore been puzzling. We have analyzed GAGs in C. elegans using reversed-phase ion-pairing HPLC, mass spectrometry and immunohistochemistry. Our analyses included wild type C. elegans but also a mutant lacking two HS sulfotransferases (hst-6 hst-2), as we suspected that the altered HS structure could boost CS sulfation. We could indeed detect sulfated CS in both wild type and mutant nematodes. While 4-O-sulfation of galactosamine dominated, we also detected 6-O-sulfated galactosamine residues. Finally, we identified the product of the gene C41C4.1 as a C. elegans CS-sulfotransferase and renamed it chst-1 (CarboHydrate SulfoTransferase) based on loss of CS-4-O-sulfation in a C41C4.1 mutant and in vitro sulfotransferase activity of recombinant C41C4.1 protein. We conclude that C. elegans indeed manufactures CS, making this widely used nematode an interesting model for developmental studies involving CS.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Tabea
authors.initials: T
authors.lastname: Dierker
authors.affiliation: Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University Medical Campus, Boston, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Organismal Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Haitina
authors.affiliation: Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University Medical Campus, Boston, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zaia
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hinas
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Kjellén
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000096:biosynthesis* / Q000235:genetics; D013058:Mass Spectrometry; D009154:Mutation; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002809:Chondroitin Sulfates; D015238:Sulfotransferases; C021350:heparitin sulfotransferase