TY - JOUR
T1 - Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans
AU - Mizuguchi, Souhei
AU - Uyama, Toru
AU - Kitagawa, Hiroshi
AU - Nomura, Kazuko H.
AU - Dejima, Katsufumi
AU - Gengyo-Ando, Keiko
AU - Mitani, Shohei
AU - Sugahara, Kazuyuki
AU - Nomura, Kazuya
N1 - Funding Information:
Acknowledgements We thank T. Stiernagle and the Caenorhabditis Genetics Center for all worms and E. coli strains, and Y. Kohara for the yk clones. K.N. was supported by PRESTO and SORSTof the Japan Science and Technology Corporation (JST). S.M. and K.H.N. were supported partly by Sasakawa Scientific Research Grant (JSS). The work at Kobe Pharmaceutical University was supported in part by a Science Research Promotion Fund from the Japan Private School Promotion Foundation, and by Grants-in-Aid for Scientific Research C (to H.K.) and Scientific Research B (to K.S.) from the Ministry of Education, Science, Sports and Culture of Japan.
Funding Information:
Acknowledgements We thank B. Castor for help with DNA sequencing; Y. Kohara for the cDNA clones yk20dy and yk21g9; A. Coulson for cosmids; J. Brown for the GlcAb1,3Gal-O-NM acceptor; B. Zak for N-acetylheparosan acceptor; the Glycotechnology Core at UCSD (supported by an NIH grant) for the preparation of UDP-[1-3H]GlcA; and B. Galvin and I. Perez de la Cruz for reading the manuscript. This work was supported by NIH grants (to H.R.H. and J.D.E.). S.K.O. was supported by an NIH training grant. H.R.H. is an Investigator of the Howard Hughes Medical Institute.
PY - 2003/5/22
Y1 - 2003/5/22
N2 - Glycosaminoglycans such as heparan sulphate and chondroitin sulphate are extracellular sugar chains involved in intercellular signalling. Disruptions of genes encoding enzymes that mediate glycosaminoglycan biosynthesis have severe consequences in Drosophila and mice. Mutations in the Drosophila gene sugarless, which encodes a UDP-glucose dehydrogenase, impair developmental signalling through the Wnt family member Wingless, and signalling by the fibroblast growth factor and Hedgehog pathways. Heparan sulphate is involved in these pathways, but little is known about the involvement of chondroitin. Undersulphated and oversulphated chondroitin sulphate chains have been implicated in other biological processes, however, including adhesion of erythrocytes infected with malaria parasite to human placenta and regulation of neural development. To investigate chondroitin functions, we cloned a chondroitin synthase homologue of Caenorhabditis elegans and depleted expression of its product by RNA-mediated interference and deletion mutagenesis. Here we report that blocking chondroitin synthesis results in cytokinesis defects in early embryogenesis. Reversion of cytokinesis is often observed in chondroitin-depleted embryos, and cell division eventually stops, resulting in early embryonic death. Our findings show that chondroitin is required for embryonic cytokinesis and cell division.
AB - Glycosaminoglycans such as heparan sulphate and chondroitin sulphate are extracellular sugar chains involved in intercellular signalling. Disruptions of genes encoding enzymes that mediate glycosaminoglycan biosynthesis have severe consequences in Drosophila and mice. Mutations in the Drosophila gene sugarless, which encodes a UDP-glucose dehydrogenase, impair developmental signalling through the Wnt family member Wingless, and signalling by the fibroblast growth factor and Hedgehog pathways. Heparan sulphate is involved in these pathways, but little is known about the involvement of chondroitin. Undersulphated and oversulphated chondroitin sulphate chains have been implicated in other biological processes, however, including adhesion of erythrocytes infected with malaria parasite to human placenta and regulation of neural development. To investigate chondroitin functions, we cloned a chondroitin synthase homologue of Caenorhabditis elegans and depleted expression of its product by RNA-mediated interference and deletion mutagenesis. Here we report that blocking chondroitin synthesis results in cytokinesis defects in early embryogenesis. Reversion of cytokinesis is often observed in chondroitin-depleted embryos, and cell division eventually stops, resulting in early embryonic death. Our findings show that chondroitin is required for embryonic cytokinesis and cell division.
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U2 - 10.1038/nature01635
DO - 10.1038/nature01635
M3 - Article
C2 - 12761550
AN - SCOPUS:0038485622
SN - 0028-0836
VL - 423
SP - 443
EP - 448
JO - Nature
JF - Nature
IS - 6938
ER -