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Organized cannabinoid receptor distribution in neurons revealed by super-resolution fluorescence imaging

By Hui Li, Jie Yang, Tian Cuiping, Min Diao, Quan Wang, Simeng Zhao, Shanshan Li, Fangzhi Tan, Tian Hua, Chao-Po Lin, Dylan Deska-Gauthier, Garth Thompson, Ying Zhang, Tong Wang, Wenqing Shui, Zhi-Jie Liu, Guisheng Zhong

Posted 25 Mar 2020
bioRxiv DOI: 10.1101/2020.03.22.002642 (published DOI: 10.1038/s41467-020-19510-5)

G-protein-coupled receptors (GPCRs) play important roles in cellular functions. However, their intracellular organization is largely unknown. Through investigation of the cannabinoid receptor 1 (CB1), we discovered periodically repeating clusters of CB1 hotspots within the axons of neurons. We observed these CB1 hotspots interact with the membrane-associated periodic skeleton (MPS) forming a complex crucial in the regulation of CB1 signaling. Furthermore, we found that CB1 hotspot periodicity increased upon CB1 agonist application, and these activated CB1 displayed less dynamic movement compared to non-activated CB1. Our results suggest that CB1 forms periodic hotspots organized by the MPS as a mechanism to increase signaling efficacy when being activated.

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