Regulation of channel activities by glycosylation during acquirement of neural plasticity

我提出了一个假设，即神经可塑性的多样性是由蛋白质的翻译后修饰来调节的。我一直专注于大脑中唾液酸糖蛋白的研究，并在体内和体外研究唾液酸化在神经可塑性中的作用。我们发现，点燃刺激诱导了小鼠结构神经可塑性的获得，并诱导了海马区和接受海马区投射的丘脑前核中α2，3-唾液酸基转移酶的表达增加。由于α2，3-唾液酸基转移酶是几种通道唾液酸化的关键酶，我们计划研究该酶在通道功能与结构神经可塑性变化之间的关系。首先，我们准备了条件基因敲除小鼠来对抗这个大的酶基因。在两年的时间里，我们完成了小鼠模型的制作。同时，第二，为了了解唾液酸化对通道功能的影响，我们计划研究树枝和突触之间的膜动力学。在这一过程中，我们确定了从浮筏膜到突触膜分离的条件，我们发现在浮筏膜和突触膜之间的几个通道上存在不同的葡聚糖形态。这给了我开始研究α2，3-唾液酸基转移酶缺陷小鼠脑内通道膜动力学的机会。

I have proposed a hypothesis that diversity of neural plasticity is regulated by post-translational modification of proteins. I have focused on sialylated glycoproteins in brain and have investigated on sialylation in neural plasticity in vivo and in vitro. We have found that kindling stimulation of mice induced acquirement of structural neural plasticity and the acquirement induced increase of a α2,3-sialyltransferase expressions in the hippocampus and the anterior thalamic nuclei which receive projects from the hippocampus. As the α2,3-sialyltransferase is a key enzyme for sialylation of several channels, we planed to investigate on effects of the enzyme on how channel functions are correlated with changes of structural neural plasticity. First, we prepared conditional knock-out mice against the enzyme gene in this grand. During two years, we finished to make the model mice. At the same time, second, we planed to examine membrane dynamics between rafts and synapses for understanding effects of sialylation on channel functions. During this grand, we determined conditions to separate from raft to synapse membranes and we found different glycan forms on several channels between raft and synapse membranes. This grand gave a chance that I start to investigate membrane dynamics of channels in α2,3-sialyltransferase deficient mouse brain.