Protective effects of polysialic acid on proteolytic cleavage of FGF2 and proBDNF/BDNF
Protective effects of polysialic acid on proteolytic cleavage of FGF2 and proBDNF/BDNF
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DOI：
10.1093/glycob/cwv049
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发表时间：
2015-10-01
期刊：
影响因子：
4.3
通讯作者：
Sato, Chihiro
中科院分区：
文献类型：
--
作者：
Hane, Masaya;Matsuoka, Shuhei;Sato, Chihiro
聚唾液酸(PolySia)是一种线性唾液酸聚合物，可修饰脊椎动物大脑中的神经细胞黏附分子(NCAM)。PolySia是一种大而独特的分子，起着细胞间相互作用的负调节作用。最近，我们证实PolySia可以特异性地结合成纤维细胞生长因子2(FGF2)和BDNF；然而，PolySia对这些蛋白质的蛋白水解性切割的保护作用尚不清楚，尽管肝素/硫酸肝素已被证明削弱了FGF2被胰酶切割。在这里，我们分析了PolySia对FGF2和proBDNF/BDNF蛋白水解性切割的保护作用。我们发现，PolySIA通过NCAM上延伸的PolySia链与FGF2的特异性结合来保护完整的FGF2免受胰酶活性的影响。寡聚SIA还通过与NCAM上的寡聚SIA链结合而损害纤溶酶对ProBDNF的处理。此外，先前从精神分裂症患者中发现的由突变的多唾液酸转移酶ST8SIA2/STX(SNP7)合成的PolySia结构与正常的ST8SIA2产生的PolySIA相比，这些功能受到损害。综上所述，这些数据表明，PolySIA对FGF2和ProBDNF的保护作用可能参与了这些神经活性分子浓度的调节。
Polysialic acid (polySia) is a linear polymer of sialic acid that modifies neural cell adhesion molecule (NCAM) in the vertebrate brain. PolySia is a large and exclusive molecule that functions as a negative regulator of cell-cell interactions. Recently, we demonstrated that polySia can specifically bind fibroblast growth factor 2 (FGF2) and BDNF; however, the protective effects of polySia on the proteolytic cleavage of these proteins remain unknown, although heparin/heparan sulfate has been shown to impair the cleavage of FGF2 by trypsin. Here, we analyzed the protective effects of polySia on the proteolytic cleavage of FGF2 and proBDNF/BDNF. We found that polySia protected intact FGF2 from tryptic activity via the specific binding of extended polySia chains on NCAM to FGF2. Oligo/polySia also functioned to impair the processing of proBDNF by plasmin via binding of oligo/polySia chains on NCAM. In addition, the polySia structure synthesized by mutated polysialyltransferase, ST8SIA2/STX(SNP7), which was previously identified from a schizophrenia patient, was impaired for these functions compared with polySia produced by normal ST8SIA2. Taken together, these data suggest that the protective effects of polySia toward FGF2 and proBDNF may be involved in the regulation of the concentrations of these neurologically active molecules.