Regulation of Endocannabinoid Signaling

Posted by Digital Strategies (Div of Comm) on Monday, June 4, 2018 in Uncategorized.

Calcium signaling drives many biochemical processes in dendritic spines, including synthesis of the major brain endocannabinoid, 2-arachidonylglycerol (2-AG), by diacylglycerol lipase-alpha (DGLa). We found that DGLa is another CaMKAP, and that CaMKII phosphorylates DGLa to inhibit 2-AG synthesis. Thus, in addition to activating DGLa, calcium recruits CaMKII to restrain synaptic 2-AG signaling, limiting the resulting short-term depression of synaptic transmission in the striatum, and modulating overall motor function. Ongoing studies are using lentiviral-based strategies and mouse genetics to manipulate DGLa and protein kinase activities to investigate the impact on striatal synaptic transmission and motor function.