The endocannabinoid system (ECS) acts as a negative feedback mechanism to suppress synaptic transmission and plays a major role in a diverse range of brain functions including, for example, the regulation of mood, energy balance, and learning and memory. The function and dysfunction of the ECS are strongly implicated in multiple psychiatric, neurological, and neurodegenerative diseases. Cannabinoid type 1 receptor (CB1R) is the most abundant G protein-coupled receptor (GPCR) expressed in the brain and, as for any synaptic receptor, CB1R needs to be in the right place at the right time to respond appropriately to changing synaptic circumstances. While CB1R is found intracellularly throughout neurons, its surface expression is highly polarized to the axonal membrane, consistent with its functional expression at presynaptic sites. Surprisingly, despite the importance of CB1R, the interacting proteins and molecular mechanisms that regulate the highly polarized distribution and function of CB1R remain relatively poorly understood. Here we set out what is currently known about the trafficking pathways and protein interactions that underpin the surface expression and axonal polarity of CB1R, and highlight key questions that still need to be addressed.

内源性大麻素系统（ECS）充当抑制突触传递的负反馈机制，并且在各种大脑功能（包括情绪调节，能量平衡以及学习和记忆）中发挥重要作用。ECS的功能和功能异常与多种精神病，神经病和神经退行性疾病密切相关。大麻素1型受体（CB1R）是大脑中表达最丰富的G蛋白偶联受体（GPCR），对于任何突触受体，CB1R必须在正确的时间，正确的位置放置在正确的位置，以对不断变化的突触环境做出适当反应。虽然CB1R在整个神经元的细胞内发现，但其表面表达高度偏向轴突膜，与其在突触前位点的功能性表达一致。出奇，尽管CB1R的重要性，但调节CB1R高度极化分布和功能的相互作用蛋白和分子机制仍然知之甚少。在这里，我们列出了目前有关CB1R的表面表达和轴突极性基础的运输途径和蛋白质相互作用的已知信息，并重点指出了仍需解决的关键问题。