Sulfation patterns of chondroitin sulfate regulate neural plasticity

2015 Fiscal Year Final Research Report

• Project/Area Number: 25860057
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Nagoya University
• Principal Investigator: Miyata Shinji 名古屋大学, 生物機能開発利用研究センター, 助教 (60533792)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: プロテオグリカン / コンドロイチン硫酸 / ペリニューロナルネット / 神経可塑性

Outline of Final Research Achievements

Perineuronal nets (PNNs) are lattice-like extracellular matrix structures composed of chondroitin sulfate proteoglycans (CSPGs). It has been shown that sulfation patterns of chondroitin sulfate (CS) chains on CSPGs influenced neural plasticity. However, the mechanism of PNN formation regulated by CS sulfation remains unknown. In this study, I found that overexpression of chondroitin 6-sulfotransferase-1 (C6ST-1) selectively decreased aggrecan, a major CSPG in PNNs, in the aged brain without affecting other PNN components. Overexpression of 6-sulfation primarily impaired accumulation of aggrecan in PNNs. Increased 6-sulfation accelerated proteolysis of aggrecan by a disintegrin and metalloproteinase domain with thrombospondin motif protease. These results indicate that sulfation patterns of CS chains on aggrecan influenced the stability of the CSPG, thereby regulating formation of PNNs and neural plasticity.

Free Research Field

神経糖鎖生物学