Polysialic acid (polySia) is mainly found as a modification of neural cell adhesion molecule (NCAM) in whole embryonic brains, as well as restricted areas of adult vertebrate brains, including the hippocampus. PolySia shows not only repulsive effects on NCAM-involved cell–cell interactions due to its bulky and hydrated properties, but also attractive effects on the interaction with neurologically active molecules, which exerts a reservoir function. Two different polysialyltransferases, ST8SIA2 and ST8SIA4, are involved in the synthesis of polySia chains; however, to date, the differences of the properties between polySia chains synthesized by these two enzymes remain unknown. In this study, to clarify this point, we first prepared polySia-NCAMs from HEK293 cells stably expressing ST8SIA4 and ST8SIA2, or ST8SIA2 (SNP-7), a mutant ST8SIA2 derived from a schizophrenia patient. The conventional sensitive chemical and immunological characterizations showed that the quantity and quality (structural features) of polySia are not so much different between ST8SIA4- and ST8SIA2-synthesized ones, apart from those of ST8SIA2 (SNP-7). Then, we assessed the homophilic and heterophilic interactions mediated by polySia-NCAM by adopting a surface plasmon resonance measurement as an in vitro analytical method. Our novel findings are as follows: (i) the ST8SIA2- and ST8SIA4-synthesized polySia-NCAMs exhibited different attractive and repulsive effects than each other; (ii) both polySia- and oligoSia-NCAMs synthesized by ST8SIA2 were able to bind polySia-NCAMs; (iii) the polySia-NCAM synthesized by a ST8SIA2 (SNP-7) showed markedly altered attractive and repulsive properties. Collectively, polySia-NCAM is suggested to simultaneously possess both attractive and repulsive properties that are highly regulated by the two polysialyltransferases.

中文翻译：

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聚唾液酸转移酶ST8SIA2和ST8SIA4合成的聚唾液酸的不同性质

聚唾液酸（polySia）主要被发现是整个胚胎大脑以及成年脊椎动物大脑（包括海马）的受限区域中神经细胞粘附分子（NCAM）的修饰。PolySia不仅由于其庞大和水合的特性而对NCAM参与的细胞间相互作用具有排斥作用，而且对与具有储库功能的神经活性分子的相互作用也具有吸引作用。两种不同的聚唾液酸转移酶ST8SIA2和ST8SIA4参与了polySia链的合成。然而，迄今为止，由这两种酶合成的polySia链之间的性质差异仍然未知。在这项研究中，为了澄清这一点，我们首先从稳定表达ST8SIA4和ST8SIA2或ST8SIA2（SNP-7）的HEK293细胞制备了polySia-NCAM，来自精神分裂症患者的突变体ST8SIA2。常规的敏感化学和免疫学表征表明，除了ST8SIA2（SNP-7）之外，ST8SIA4-和ST8SIA2合成的polySia的数量和质量（结构特征）没有太大差异。然后，我们通过采用表面等离振子共振测量作为一种体外分析方法，评估了由polySia-NCAM介导的同型和异型相互作用。我们的新发现如下：（i）ST8SIA2-和ST8SIA4合成的polySia-NCAM表现出彼此不同的吸引力和排斥力；（ii）由ST8SIA2合成的polySia-和oligoSia-NCAM都能够结合polySia-NCAM；（iii）由ST8SIA2（SNP-7）合成的polySia-NCAM显示出明显改变的吸引和排斥特性。