Manipulation of Arabidopsis Fatty Acid Amide Hydrolase Expression Modifies Plant Growth and Sensitivity to N-Acylethanolamines

In vertebrates, the endocannabinoid signaling pathway is an important lipid regulatory pathway that modulates a variety of physiological and behavioral processes.  N -Acylethanolamines (NAEs) comprise a group of fatty acid derivatives that function within this pathway, and their signaling activity is terminated by an enzyme called fatty acid amide hydrolase (FAAH), which hydrolyzes NAEs to ethanolamine and their corresponding free fatty acids. Bioinformatic approaches led to the identification of plant homologues of FAAH that are capable of hydrolyzing NAEs  in vitro . To better understand the role of NAEs in plants, we identified T-DNA knockouts to  Arabidopsis  FAAH ( AtFAAH ; At5g64440) and generated plants overexpressing  AtFAAH . Here we show that seeds of  AtFAAH  knockouts had elevated levels of endogenous NAEs, and seedling growth was hypersensitive to exogenously applied NAE. On the other hand, seeds and seedlings of  AtFAAH overexpressors had lower endogenous NAE content, and seedlings were less sensitive to exogenous NAE. Moreover,  AtFAAH  overexpressors displayed enhanced seedling growth and increased cell size.  AtFAAH  expression and FAAH catalytic activity increased during seed germination and seedling growth, consistent with the timing of NAE depletion during seedling establishment. Collectively, our results show that AtFAAH is one, but not the only, modulator of endogenous NAE levels in plants, and that NAE depletion likely participates in the regulation of plant growth.