Hwang Ho-Yon, Olson Sara K, Esko Jeffrey D, Horvitz H Robert
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Room 68-425, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Nature. 2003 May 22;423(6938):439-43. doi: 10.1038/nature01634.
Defects in glycosaminoglycan biosynthesis disrupt animal development and can cause human disease. So far much of the focus on glycosaminoglycans has been on heparan sulphate. Mutations in eight squashed vulva (sqv) genes in Caenorhabditis elegans cause defects in cytokinesis during embryogenesis and in vulval morphogenesis during postembryonic development. Seven of the eight sqv genes have been shown to control the biosynthesis of the glycosaminoglycans chondroitin and heparan sulphate. Here we present the molecular identification and characterization of the eighth gene, sqv-5. This gene encodes a bifunctional glycosyltransferase that is probably localized to the Golgi apparatus and is responsible for the biosynthesis of chondroitin but not heparan sulphate. Our findings show that chondroitin is crucial for both cytokinesis and morphogenesis during C. elegans development.
糖胺聚糖生物合成缺陷会扰乱动物发育,并可导致人类疾病。到目前为止,对糖胺聚糖的关注大多集中在硫酸乙酰肝素上。秀丽隐杆线虫中八个压扁外阴(sqv)基因的突变会导致胚胎发育期间的胞质分裂缺陷以及胚胎后发育期间的外阴形态发生缺陷。已证明八个sqv基因中的七个控制着糖胺聚糖软骨素和硫酸乙酰肝素的生物合成。在这里,我们展示了第八个基因sqv-5的分子鉴定和特征。该基因编码一种双功能糖基转移酶,可能定位于高尔基体,负责软骨素而非硫酸乙酰肝素的生物合成。我们的研究结果表明,软骨素对秀丽隐杆线虫发育过程中的胞质分裂和形态发生都至关重要。