Format

Send to

Choose Destination
See comment in PubMed Commons below
Neuropharmacology. 2016 Aug;107:201-14. doi: 10.1016/j.neuropharm.2016.03.008. Epub 2016 Mar 9.

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

Author information

1
Institute of Molecular Genetics, Academy of Science of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic.
2
Institut de Génomique Fonctionnelle, University of Montpellier 1 and 2, Montpellier, France.
3
Institute of Molecular Genetics, Academy of Science of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic. Electronic address: blahos@img.cas.cz.

Abstract

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, β-arrestin associated signaling is changed profoundly, most likely as a consequence of the prevention of the receptor's internalization elicited by SGIP1.

KEYWORDS:

Bias signaling; Cannabinoid receptor 1; G-protein coupled receptors; Protein-protein interactions; Receptor endocytosis; Seven transmembrane receptors

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center