Membrane lipids are key modulators of the endocannabinoid-hydrolase FAAH

• DOI: 10.1042/bj20130960
• Publication Date: 2013-11-13T09:48:46Z
• Authors: Enrico Dainese; Gianni De Fabritiis; Annalaura Sabatucci; Sergio Oddi; Clotilde Beatrice...; Chiara Di Pancrazio; Toni Giorgino; Nathaniel Stanley; Michele Del Carlo; Benjamin F. Cravatt; Mauro Maccarrone
• Keywords: Anandamide

Lipid composition is expected to play an important role in modulating membrane enzyme activity, particular if the substrates are themselves lipid molecules. A paradigmatic case FAAH (fatty acid amide hydrolase), critical terminating endocannabinoid signalling and therapeutic target. In present study, using a combined experimental computational approach, we show that lipids modulate structure, subcellular localization activity of FAAH. We report dimer stabilized by bilayer shows higher membrane-binding affinity enzymatic within membranes containing both cholesterol natural substrate AEA (anandamide). Additionally, co-localization cholesterol, mouse neuroblastoma cells suggests mechanism through which increases accessibility