祖先型ニューレキシンの構造・機能解析

该项目阐明了神经素（Nrxns）在神经系统早期进化中的作用。Nrxns是突触前细胞黏附的核心分子，在化学突触中具有重要的功能，但其起源和进化历史尚不清楚。我采用了多学科的方法，首次对双侧体外nrxn介导的神经元信号进行了表征。我展示了在刺胞菌（Nematostella vectensis）中，刺胞菌是最接近双胞菌的外群，敲低神经元表达的Nrxns会导致肌肉收缩等异常行为。我证明了N. vectensis的神经Nrxns对经典化学递质（如谷氨酸、甘氨酸）的传递是必需的，但对神经肽信号传导则不是必需的。此外，vectensis Nrxns的非神经功能可能解释了该蛋白家族如何以及为什么被用于早期神经系统的突触机制。广泛表达的Nrxns的功能分析揭示了它们在异源细胞-细胞粘附中起主要作用；特别是外胚层和内胚层上皮细胞之间的连接的维持。到2021财年年底，我已经完成了所有的实验。在FY2022（4 - 10月），我对正在准备投稿的稿件进行了额外的实验。

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.