Selective regulation of presynaptic receptors by SGIP1

Abstract

Selective regulation of presynaptic receptors by SGIP1 Abstract Cannabinoid receptor 1 (CB1R) is involved in a plethora of physiological processes, such as memory formation, motor coordination, anxiety, pain perception, and immune response. The properties of many minor cannabinoid receptor ligands remain unknown. The activity of CB1R is regulated by Src homology 3-domain growth factor receptor-bound 2-like endophilin interacting protein 1 (SGIP1). Several splice variants of SGIP1 have been described in the literature, but their specific functional roles are unknown. SGIP1 inhibits CB1R internalization and enhances β-arrestin and G protein-coupled receptor kinase 3 (GRK3) interactions with the receptor. In mice, deletion of Sgip1 results in altered mood-related behavior, decreased anxiety- like behavior, and decreased acute nociception. In this work, we tested the effect of Sgip1 deletion on chronic nociception. We further explored the pattern of alternative splicing of Sgip1 in the brain. In addition, we tested the effect of the minor cannabinoid hexahydrocannabinol (HHC) on CB1R signaling. We found that Sgip1 deletion results in an increase in chronic nociception in male but not in female mice. We detected 15 Sgip1 splice variants in the mouse brain. The Sgip1 exons that undergo alternative splicing encode...