神经系统中大麻素CB1受体与周期性细胞骨架相互作用的机制和功能研究

大麻素CB1受体是中枢神经系统中表达最丰富的GPCR之一，在多种生理及病理的调节中发挥着重要作用。然而，CB1受体在神经元中的超微分布特点及与细胞骨架蛋白网络的相互作用的机制和功能尚不清楚。在我们的前期研究中发现，CB1受体在神经元轴突上呈周期性分布，并具有与细胞骨架蛋白相似的周期性分布规律。据此，我们提出CB1受体与周期性细胞骨架存在一定的相互作用，并且这种相互作用能进一步介导CB1受体的下游信号通路。本课题拟采用超高分辨显微成像技术并结合活细胞成像，钙成像，核磁共振成像，分子生物学，生化细胞学，行为学手段研究CB1受体与周期性骨架蛋白的相互作用的分子机制，从细胞到个体跨尺度探索其相互作用的功能意义，为进一步阐释GPCRs在时空上的作用和机制，神经元周期性骨架结构的功能提供依据。

The cannabinoid receptor 1 (CB1) is one of the most widespread GPCRs expressed in central nervous system, which mediate several key biological functions. However, the ultrastructure of CB1 and the interaction with cytoskeleton in the nervous system remain controversial. Our preliminary data show that CB1 display a periodic 190-nm ultrastructure in axons with super-resolution fluorescence imaging method, resembling a previously discovered periodic cytoskeletal structure in neurons. Hereby, we raise the hypothesis that CB1 interact with membrane-associated periodic skeleton in axons and this interaction affected the cellular signaling of CB1. The current study intent to combine the super-resolution fluorescent microscopy, calcium imaging, magnetic resonance imaging, molecular biological methods and behavior test to investigate the molecular mechanism and cross-scaled function of interaction between CB1 and periodic cytoskeletal proteins. The novel cellular structure of CB1 and its association with cytoskeleton may shed light on the role and mechanism of GPCRs in space and time, and to provide further insights into the function of periodic skeleton structure in neurons.