A role for ERp57 in the regulation of anandamide metabolism

Abstract

The cannabinoid field is currently an active research area due to a proposed role for endogenous cannabinoids, such as anandamide (AEA), in various physiological processes. AEA is synthesized on‐demand and released into the extracellular space, where it acts as an agonist at both the central and peripheral nervous system cannabinoid receptors CB1 and CB2, respectively. To cease signaling, AEA is transported into cells, where it is metabolized by the enzyme fatty acid amide hydrolase (FAAH1). However, very little is known regarding AEA transport. Our lab has previously identified caveolae‐dependent endocytosis as a mechanism for AEA transport. We recently showed that the protein ERp57 localizes to caveolae during AEA transport. Interestingly, the transcription factor STAT3, which interacts with ERp57 and has been implicated in the regulation of FAAH1 gene expression, localizes to caveolae in its inactive form. We propose that in response to AEA transport, ERp57 and STAT3 work together to up‐regulate FAAH1 gene transcription. Such increases in FAAH1 expression levels have previously been associated with increased AEA transport. We are using RNAi technology to explore the role of ERp57 in STAT3‐regulated FAAH1 transcription. Additionally, we are using various techniques to identify changes in both FAAH1 expression and STAT3 activation in response to AEA uptake. Research funded by NIH Grant R21DA018844.