Chondroitin 4-O-Sulfotransferase is indispensable for sulfation of chondroitin and plays an important role in maintaining normal life span and oxidative stress responses in nematodes

Tomomi Izumikawa, Katsufumi Dejima, Yukiko Watamoto, Kazuko H. Nomura, Nanako Kanaki, Marika Rikitake, Mai Tou, Daisuke Murata, Eri Yanagita, Ai Kano, Shohei Mitani, Kazuya Nomura, Hiroshi Kitagawa

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Chondroitin sulfate (CS)/chondroitin (Chn) chains are indispensable for embryonic cell division and cytokinesis in the early developmental stages in Caenorhabditis elegans and mice, whereas heparan sulfate (HS) is essential for axon guidance during nervous system development. These data indicate that the fundamental functions of CS and HS are conserved from worms to mammals and that the function of CS/Chn differs from that of HS. Although previous studies have shown that C. elegans produces HS and non-sulfated Chn, whether the organism produces CS remains unclear. Here, we demonstrate that C. elegans produces a small amount of 4-O-sulfated Chn and report the identification of C41C4.1, an orthologue of the human chondroitin 4-O-sulfotransferase gene. Loss of C41C4.1 in C. elegans resulted in a decline in 4-O-sulfation of CS and an increase in the number of sulfated units in HS. C41C4.1 deletion mutants exhibited reduced survival rates after synchronization with sodium hypochlorite. Collectively, these results show for the first time that CS glycans are present in C. elegans and that the Chn 4-O-sulfotransferase responsible for the sulfation plays an important role in protecting nematodes from oxidative stress.

Original languageEnglish
Pages (from-to)23294-23304
Number of pages11
JournalJournal of Biological Chemistry
Issue number44
Publication statusPublished - Oct 28 2016


All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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