SGIP1 alters internalization and modulates signaling of activated cannabinoid receptor 1 in a biased manner

0471838 - ÚMG 2017 RIV GB eng J - Článek v odborném periodiku
Hájková, Alena - Techlovská, Šárka - Dvořáková, Michaela - Chambers, Jayne Nicole - Kumpošt, Jiří - Hubálková, Pavla - Prezeau, L. - Blahoš, Jaroslav
SGIP1 alters internalization and modulates signaling of activated cannabinoid receptor 1 in a biased manner.
Neuropharmacology. Roč. 107, léto (2016), s. 201-214. ISSN 0028-3908. E-ISSN 1873-7064
Grant CEP: GA ČR GAP303/12/2408
Institucionální podpora: RVO:68378050
Klíčová slova: Seven transmembrane receptors * G-protein coupled receptors * Cannabinoid receptor 1 * Protein-protein interactions * Bias signaling * Receptor endocytosis
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 5.012, rok: 2016

Many diseases of the nervous system are accompanied by alterations in synaptic functions. Synaptic plasticity mediated by the endogenous cannabinoid system involves the activation of the cannabinoid receptor 1 (CB1R). The principles of CB1R signaling must be understood in detail for its therapeutic exploration. We detected the Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1) as a novel CB1R partner. SGIP1 is functionally linked to clathrin-mediated endocytosis and its overexpression in animals leads to an energy regulation imbalance resulting in obesity. We report that SGIP1 prevents the endocytosis of activated CB1R and that it alters signaling via the CB1R in a biased manner. CB1R mediated G-protein activation is selectively influenced by SGIP1, arrestin associated signaling is changed profoundly, most likely as a consequence of the prevention of the receptor's internalization elicited by SGIP1. (C) 2016 The Authors. Published by Elsevier Ltd.
Trvalý link: http://hdl.handle.net/11104/0269162