Mizuguchi Souhei, Uyama Toru, Kitagawa Hiroshi, Nomura Kazuko H, Dejima Katsufumi, Gengyo-Ando Keiko, Mitani Shohei, Sugahara Kazuyuki, Nomura Kazuya
Department of Biology, Faculty of Sciences 33, Kyushu University, Fukuoka 812-8581, Japan.
Nature. 2003 May 22;423(6938):443-8. doi: 10.1038/nature01635.
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, impairs 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.
诸如硫酸乙酰肝素和硫酸软骨素之类的糖胺聚糖是参与细胞间信号传导的细胞外糖链。编码介导糖胺聚糖生物合成的酶的基因发生破坏,在果蝇和小鼠中会产生严重后果。果蝇基因“无糖”(sugarless)发生突变,该基因编码一种UDP - 葡萄糖脱氢酶,会损害通过Wnt家族成员无翅(Wingless)的发育信号传导,以及成纤维细胞生长因子和刺猬(Hedgehog)信号通路的信号传导。硫酸乙酰肝素参与这些信号通路,但对于硫酸软骨素的参与情况知之甚少。然而,硫酸化不足和硫酸化过度的硫酸软骨素链已被证明与其他生物过程有关,包括感染疟原虫的红细胞与人胎盘的黏附以及神经发育的调节。为了研究硫酸软骨素的功能,我们克隆了秀丽隐杆线虫的一种硫酸软骨素合酶同源物,并通过RNA介导的干扰和缺失诱变来降低其产物的表达。在此我们报告,阻断硫酸软骨素合成会导致早期胚胎发育过程中的胞质分裂缺陷。在硫酸软骨素缺失的胚胎中经常观察到胞质分裂的逆转,最终细胞分裂停止,导致早期胚胎死亡。我们的研究结果表明,硫酸软骨素是胚胎胞质分裂和细胞分裂所必需的。