Chondroitin 6-Sulfation Regulates Perineuronal Net Formation by Controlling the Stability of Aggrecan.
Chondroitin 6-Sulfation Regulates Perineuronal Net Formation by Controlling the Stability of Aggrecan.
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DOI：
10.1155/2016/1305801
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发表时间：
2016
影响因子：
3.1
通讯作者：
Kitagawa H
中科院分区：
文献类型：
--
作者：
Miyata S;Kitagawa H
神经元周网（PNN）是由硫酸软骨素蛋白聚糖（CSPG）组成的网格状细胞外基质结构。PNNs的出现与神经可塑性的下降相平行，PNNs的破坏重新激活了成年大脑中的神经可塑性。我们以前报道，硫酸软骨素（CS）链的硫酸化模式的CSPGs影响PNN的形成和神经可塑性。然而，CS硫酸化调控PNN形成的机制仍不清楚。在这里，我们发现，软骨素6-磺基转移酶-1（C6 ST-1），催化CS链的6-硫酸化，选择性地减少聚集蛋白聚糖，一个主要的CSPG在PNN，在老年人的大脑，而不影响其他PNN组件。C6 ST-1的过度表达降低了弥漫性和PNN相关聚集蛋白聚糖。C6 ST-1增加了CS链重复二糖区和连接区的6-硫酸化。6-硫酸化的过度表达主要损害聚集蛋白聚糖在PNN中的积累，而其他PNN组分的缩合不受影响。最后，我们发现，增加6-硫酸化加速蛋白水解的聚集蛋白聚糖的解整合素和金属蛋白酶域与血小板反应蛋白基序（ADAMTS）蛋白酶。两者合计，我们的研究结果表明，CS链的硫酸化模式的聚集蛋白聚糖的影响CSPG的稳定性，从而调节PNNs和神经可塑性的形成。
Perineuronal nets (PNNs) are lattice-like extracellular matrix structures composed of chondroitin sulfate proteoglycans (CSPGs). The appearance of PNNs parallels the decline of neural plasticity, and disruption of PNNs reactivates neural plasticity in the adult brain. We previously reported that sulfation patterns of chondroitin sulfate (CS) chains on CSPGs influenced the formation of PNNs and neural plasticity. However, the mechanism of PNN formation regulated by CS sulfation remains unknown. Here we found that overexpression of chondroitin 6-sulfotransferase-1 (C6ST-1), which catalyzes 6-sulfation of CS chains, selectively decreased aggrecan, a major CSPG in PNNs, in the aged brain without affecting other PNN components. Both diffuse and PNN-associated aggrecans were reduced by overexpression of C6ST-1. C6ST-1 increased 6-sulfation in both the repeating disaccharide region and linkage region of CS chains. Overexpression of 6-sulfation primarily impaired accumulation of aggrecan in PNNs, whereas condensation of other PNN components was not affected. Finally, we found that increased 6-sulfation accelerated proteolysis of aggrecan by a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) protease. Taken together, our results indicate that sulfation patterns of CS chains on aggrecan influenced the stability of the CSPG, thereby regulating formation of PNNs and neural plasticity.