Institute of Molecular Genetics of the Czech Academy of Sciences
Laboratory of Molecular Pharmacology
Endocannabinoids, cannabinoid receptor, receptors coupled to G-proteins
We detected the Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1) as a novel cannabinoid receptor 1 (CB1R) interacting partner. SGIP1 is functionally linked to clathrin-mediated endocytosis, and its overexpression in the hypothalamus leads to an energy regulation imbalance resulting in obesity in rodents. We reported that SGIP1 prevents endocytosis of activated CB1R and that it alters signalling via CB1R in a biased manner. CB1R – beta 2 arrestin-associated signalling is profoundly changed, most likely as a consequence of prevention of the receptor’s internalization, an inhibition mediated by SGIP1. To study the role of SGIP1 in vivo, we developed SGIP1 knockout mice to explore their phenotype. In a recent manuscript, we report alterations in the emotionality of SGIP1 knockout mice based on open field, elevated plus maze, and light/dark box tests. We discovered that mouse coping with despair in an inescapable situation is enhanced by SGIP1 deletion. In the tail immersion test, the antinociceptive effects of CB1R agonists were significantly enhanced in the SGIP1 knockout mice. In evaluating responses to D9-tetrahydrocannabinol in cannabinoid tetrad tests, interesting differences were found compared to wild-type mice, including modification of responses in a model of acute pain.