Chondroitin sulfate synthase-2 is necessary for chain extension of chondroitin sulfate but not critical for skeletal development.
Chondroitin sulfate synthase-2 is necessary for chain extension of chondroitin sulfate but not critical for skeletal development.
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DOI：
10.1371/journal.pone.0043806
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Watanabe H
中科院分区：
文献类型：
--
作者：
Ogawa H;Hatano S;Sugiura N;Nagai N;Sato T;Shimizu K;Kimata K;Narimatsu H;Watanabe H
硫酸软骨素（CS）是一种线性多糖，由N-乙酰基-D-半乳糖胺和D-葡萄糖醛酸残基的重复二糖单元组成，在不同位置用硫酸化残基修饰。基于其链长和硫酸化模式的结构多样性，CS在细胞粘附、形态发生、神经网络形成和细胞分裂中提供特定的生物学功能。迄今为止，已知六种糖基转移酶参与软骨素糖链的生物合成，并且已知硫酸软骨素合酶-1（CSS 1）/软骨素合酶-1和硫酸软骨素合酶-2（CSS 2）/软骨素聚合因子的异寡聚体复合物具有最强的聚合活性。在这里，我们生成并分析了CSS 2 −/−小鼠。虽然它们是可行的和肥沃的，表现出没有明显的形态异常或骨关节炎，其软骨含有CS链的长度较短，在一个类似的数量野生型。使用CSS 2 −/−软骨细胞培养系统以及CSS 1的siRNA的进一步分析揭示了长度上存在两种CS链种类，表明CS链聚合的两个步骤;即，从连接区域延伸至Mr 10，000，并进一步延伸。在那里，CSS 2主要参与扩展，而CSS 1参与扩展和启动。本研究揭示了CSS 1和CSS 2的不同功能，为阐明CS生物合成机制提供了线索。
Chondroitin sulfate (CS) is a linear polysaccharide consisting of repeating disaccharide units of N-acetyl-D-galactosamine and D-glucuronic acid residues, modified with sulfated residues at various positions. Based on its structural diversity in chain length and sulfation patterns, CS provides specific biological functions in cell adhesion, morphogenesis, neural network formation, and cell division. To date, six glycosyltransferases are known to be involved in the biosynthesis of chondroitin saccharide chains, and a hetero-oligomer complex of chondroitin sulfate synthase-1 (CSS1)/chondroitin synthase-1 and chondroitin sulfate synthase-2 (CSS2)/chondroitin polymerizing factor is known to have the strongest polymerizing activity. Here, we generated and analyzed CSS2−/− mice. Although they were viable and fertile, exhibiting no overt morphological abnormalities or osteoarthritis, their cartilage contained CS chains with a shorter length and at a similar number to wild type. Further analysis using CSS2−/− chondrocyte culture systems, together with siRNA of CSS1, revealed the presence of two CS chain species in length, suggesting two steps of CS chain polymerization; i.e., elongation from the linkage region up to Mr ∼10,000, and further extension. There, CSS2 mainly participated in the extension, whereas CSS1 participated in both the extension and the initiation. Our study demonstrates the distinct function of CSS1 and CSS2, providing a clue in the elucidation of the mechanism of CS biosynthesis.
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影响因子：
4.8
作者：
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