デジマ カツフミ   Dejima Katsufumi
  出嶋 克史
   所属   医学部 医学科
   職種   助教
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Ceramide glucosyltransferase of the nematode Caenorhabditis elegans is involved in oocyte formation and in early embryonic cell division.
掲載誌名 正式名:Glycobiology
略  称:Glycobiology
ISSNコード:1460-2423(Electronic)0959-6658(Linking)
巻・号・頁 21(6),834-48頁
著者・共著者 Nomura Kazuko H, Murata Daisuke, Hayashi Yasuhiro, Dejima Katsufumi, Mizuguchi Souhei, Kage-Nakadai Eriko, Gengyo-Ando Keiko, Mitani Shohei, Hirabayashi Yoshio, Ito Makoto, Nomura Kazuya
発行年月 2011/06
概要 Ceramide glucosyltransferase (Ugcg) [uridine diphosphate (UDP)-glucose:N-acylsphingosine D-glucosyltransferase or UDP-glucose ceramide glucosyltransferase (GlcT): EC 2.4.1.80]catalyzes formation of glucosylceramide (GlcCer) from ceramide and UDP-glucose. There is only one Ugcg gene in the mouse genome, which is essential in embryogenesis and brain development. The nematode Caenorhabditis elegans has three Ugcg genes (cgt-1, cgt-2 and cgt-3), and double RNAi of the cgt-1 and cgt-3 genes results in lethality at the L1 larval stage. In this study, we isolated knockout worms for the three genes and characterized the gene functions. Each gene product showed active enzymatic activity when expressed in GM95 cells deficient in glycosphingolipids (GSLs). When each gene function was disrupted, the brood size of the animal markedly decreased, and abnormal oocytes and multinucleated embryos were formed. The CGT-3 protein had the highest Ugcg activity, and knockout of its gene resulted in the severest phenotype. When cgt-3 RNAi was performed on rrf-1 worms lacking somatic RNAi machinery but with intact germline RNAi machinery, a number of abnormal oocytes and multinucleated eggs were observed, although the somatic phenotype, i.e., L1 lethal effects of cgt-1/cgt-3 RNAi, was completely suppressed. Cell surface expression of GSLs and sphingomyelin, which are important components of membrane domains, was affected in the RNAi-treated embryos. In the embryos, an abnormality in cytokinesis was also observed. From these results, we concluded that the Ugcg gene is indispensable in the germline and that an ample supply of GlcCer is needed for oocytes and fertilized eggs to maintain normal membranes and to proceed through the normal cell cycle.
DOI 10.1093/glycob/cwr019
文献番号 21325339