Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans
Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans
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DOI：
10.1038/nature01635
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发表时间：
2003-05-22
期刊：
影响因子：
64.8
通讯作者：
Nomura, K
中科院分区：
文献类型：
--
作者：
Mizuguchi, S;Uyama, T;Nomura, K
糖胺聚糖如硫酸乙酰肝素和硫酸软骨素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的破坏在果蝇和小鼠中具有严重后果（1-5）。果蝇无糖基因（编码UDP-葡萄糖脱氢酶）的突变会损害通过Wnt家族成员Wingless的发育信号，以及通过成纤维细胞生长因子和Hedgehog途径的信号。硫酸乙酰肝素参与这些途径（6-8），但对软骨素的参与知之甚少。然而，硫酸化不足和硫酸化过度的硫酸软骨素链与其他生物学过程有关，包括感染疟疾寄生虫的红细胞与人胎盘的粘附和神经发育的调节（9，10）。为了研究软骨素的功能，我们克隆了秀丽隐杆线虫的软骨素合酶同源物，并通过RNA介导的干扰和缺失突变来消除其产物的表达。在这里，我们报告，在早期胚胎发育中，软骨素合成受阻导致胞质分裂缺陷。在软骨素缺乏的胚胎中经常观察到胞质分裂的逆转，细胞分裂最终停止，导致早期胚胎死亡。我们的研究结果表明，软骨素是所需的胚胎胞质分裂和细胞分裂。
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(1-5). 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(6-8), 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(9,10). 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.