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

Li, Hui; Yang, Jie; Tian, Cuiping; Diao, Min; Wang, Quan; Zhao, Simeng; Li, Shanshan; Tan, Fangzhi et al. · Nat Commun · 2020

basic_science · Level V

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Abstract

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 (CB<sub>1</sub>), we discovered periodically repeating clusters of CB<sub>1</sub> hotspots within the axons of neurons. We observed these CB<sub>1</sub> hotspots interact with the membrane-associated periodic skeleton (MPS) forming a complex crucial in the regulation of CB<sub>1</sub> signaling. Furthermore, we found that CB<sub>1</sub> hotspot periodicity increased upon CB<sub>1</sub> agonist application, and these activated CB<sub>1</sub> displayed less dynamic movement compared to non-activated CB<sub>1</sub>. Our results suggest that CB<sub>1</sub> forms periodic hotspots organized by the MPS as a mechanism to increase signaling efficacy upon activation.

Medical subject headings