祖先型ニューレキシンの構造・機能解析

该项目阐明了神经毒素（Nrxns）在神经系统早期进化中的作用。Nrxns是在化学突触中具有关键功能的核心突触前细胞粘附分子，但它们的起源和进化历史仍有待探索。我采用了多学科的方法，给Nrxn介导的神经元信号外Bilateria的第一个特征。我表明，在Nematostella vectensis中，刺胞动物的一员，这是最接近的外类群Bilateria，敲低神经元表达的Nrxns导致异常行为，涉及肌肉收缩。我证明了N. Vectensis是经典化学递质的传输所必需的（例如，谷氨酸，甘氨酸），但不是神经肽信号。vectensis Nrxns的发现可能解释了这个蛋白质家族如何以及为什么在早期神经系统的突触机制中被使用。对N. vectensis的研究揭示了它们在异源细胞-细胞粘附中的主要作用;特别是在维持外胚层和内胚层上皮细胞之间的连接方面。在2022财年（4月至10月），我对准备提交的手稿进行了额外的实验。

This project elucidated the role of Neurexins (Nrxns) in the early evolution of the nervous system. Nrxns are core presynaptic cell adhesion molecules with critical functions in the chemical synapse, but their origin and evolutionary history remain underexplored. I employed a multidisciplinary approach to give the first characterization of Nrxn-mediated neuronal signaling outside Bilateria. I showed that in Nematostella vectensis, a member of Cnidaria which is the closest outgroup to Bilateria, knocking down the neuronally expressed Nrxns resulted in abnormal behaviors involving muscle contraction. I demonstrated that the neural Nrxns in N. vectensis are required for the transmission of classical chemical transmitters (e.g., glutamate, glycine) but not for neuropeptide signaling.Additionally, a non-neural function of N. vectensis Nrxns was that may explain how and why this family of proteins was employed in the synaptic machinery of the early nervous system. Functional analysis of the broadly expressed Nrxns in N. vectensis revealed their major role in heterologous cell-cell adhesion; in particular, in the maintenance of the junction between ectodermal and endodermal epithelial cells.I have completed all the experiments by the end of FY2021. In FY2022 (April to October), I performed additional experiments for the manuscript that is being prepared for submission.