AUTHOR=Angelats Edgar , Requesens Marta , Aguinaga David , Kreutz Michael R. , Franco Rafael , Navarro Gemma 

TITLE=Neuronal Calcium and cAMP Cross-Talk Mediated by Cannabinoid CB1 Receptor and EF-Hand Calcium Sensor Interactions

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 6 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2018.00067

DOI=10.3389/fcell.2018.00067

ISSN=2296-634X

ABSTRACT=Endocannabinoids are important players in neural development and function. They act via receptors, whose activation inhibits cAMP production. The aim of the paper was to look for calcium- and cAMP-signaling cross-talk mediated by cannabinoid CB1 receptors (CB1R) and the relevance of EF-hand CaM-like calcium sensors in this regard. Using a heterologous expression system, we demonstrated that CB1R interacts with calneuron-1 and NCS1 but not with caldendrin. Furthermore, the first two sensors competed for binding to the receptor in a Ca2+-dependent manner. Assays in neuronal primary cultures showed that, CB1R-NCS1 complexes predominate at basal Ca2+ levels, whereas in the presence of ionomycin, a calcium ionophore, CB1R-calneuron-1 complexes were more abundant. Signaling assays following forskolin-induced intracellular cAMP levels showed in mouse striatal neurons that binding of CB1R to NCS1 is required for CB1R induced signaling while the binding of CB1R to calneuron-1 is completely blocked signaling in response to a selective receptor agonist, arachidonyl-2-chloroethylamide.