Chondroitin 4-O-sulfotransferase-2 regulates the number of chondroitin sulfate chains initiated by chondroitin N-acetylgalactosaminyltransferase-1
Chondroitin 4-O-sulfotransferase-2 regulates the number of chondroitin sulfate chains initiated by chondroitin N-acetylgalactosaminyltransferase-1
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DOI：
10.1042/bj20111472
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发表时间：
2012-01-15
影响因子：
4.1
通讯作者：
Kitagawa, Hiroshi
中科院分区：
文献类型：
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作者：
Izumikawa, Tomomi;Koike, Toshiyasu;Kitagawa, Hiroshi
最近，已经显示ChGn-1（软骨素N-乙酰氨基半乳糖转移酶-1）的缺乏减少了CS（硫酸软骨素）链的数量，导致小鼠的骨骼发育不良。虽然这些结果表明ChGn-1调节CS链的数量，但介导这种调节的机制尚不清楚。ChGn-1被认为通过将第一个GalNAc（N-乙酰半乳糖胺）转移到CS的蛋白质连接区中的四糖来启动CS的生物合成。然而，体外软骨素聚合不发生在非还原性末端GalNAc-连接五糖结构上。在本研究中，我们表明，几种不同的异聚酶复合物组成的不同组合的四个软骨素合成酶家族成员合成更多的CS链时，半乳糖NAc连接五糖结构与非还原性末端4-O-硫酸化的CS受体。此外，C4 ST-2（软骨素4-O-磺基转移酶-2）有效地将硫酸盐从3 '-磷酸腺苷5'-磷酸硫酸盐转移到非还原性末端GalNAc-连接残基的位置4，并且CS链的数量由C4 ST-2和ChGn-1的表达水平调节。总之，本研究的结果表明，C4 ST-2在调节通过ChGn-1合成的CS水平中起关键作用。
Recently, it has been shown that a deficiency in ChGn-1 (chondroitin N-acetylgalactosaminyltransferase-1) reduced the numbers of CS (chondroitin sulfate) chains, leading to skeletal dysplasias in mice. Although these results indicate that ChGn-1 regulates the number of CS chains, the mechanism mediating this regulation is not clear. ChGn-1 is thought to initiate CS biosynthesis by transferring the first GalNAc (N-acetylgalactosamine) to the tetrasaccharide in the protein linkage region of CS. However, in vitro chondroitin polymerization does not occur on the non-reducing terminal GalNAc-linkage pentasaccharide structure. In the present study we show that several different heteromeric enzyme complexes composed of different combinations of four chondroitin synthase family members synthesized more CS chains when a GalNAc-linkage pentasaccharide structure with a non-reducing terminal 4-O-sulfation was the CS acceptor. In addition, C4ST-2 (chondroitin 4-O-sulfotransferase-2) efficiently transferred sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 4 of non-reducing terminal GalNAc-linkage residues, and the number of CS chains was regulated by the expression levels of C4ST-2 and of ChGn-1. Taken together, the results of the present study indicate that C4ST-2 plays a key role in regulating levels of CS synthesized via ChGn-1.