TY - JOUR
T1 - 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
AU - Izumikawa, Tomomi
AU - Dejima, Katsufumi
AU - Watamoto, Yukiko
AU - Nomura, Kazuko H.
AU - Kanaki, Nanako
AU - Rikitake, Marika
AU - Tou, Mai
AU - Murata, Daisuke
AU - Yanagita, Eri
AU - Kano, Ai
AU - Mitani, Shohei
AU - Nomura, Kazuya
AU - Kitagawa, Hiroshi
N1 - Funding Information:
This work was supported by a grant from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT)-supported Program for the Strategic Research Foundation at Private Universities, 2012-2016 (to H. K.) and by Grants-in-aid for Scientific Research on Innovative Areas (23110003 to H. K.), Scientific Research B (25293014 and 16H05088 to H. K.), and Scientific Research C (16K07298 to K. N.). This work was also supported by grants from the Japan Society for the Promotion of Science (JSPS) and the Core Research for Evolutional Science and Technology (CREST) Program of the Japan Science and Technology Corp. (to K. N.) and by Grant 120140 from the Mizutani Foundation (to K. N.). The authors declare that they have no conflicts of interest with respect to the contents of this article.
PY - 2016/10/28
Y1 - 2016/10/28
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M116.757328
DO - 10.1074/jbc.M116.757328
M3 - Article
C2 - 27645998
AN - SCOPUS:84993927605
VL - 291
SP - 23294
EP - 23304
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 44
ER -