In the analysis of several brain tissue samples, RGMA expression was associated with the expression of four other genes related to psychiatric traits, GRIN1, KCNIP3, FXYD6 and PTCHD1. GRIN1 was the gene that was most highly co-expressed (r=0.40) with RGMA in brain. It plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning (39). GRIN1 can tether the μ-opioid receptor (the main biological target of opioid drugs) and subsequently immobilize the μ-opioid receptor within lipid rafts (40). The overexpression of GRIN1 increases the amount of μ-opioid receptor in lipid rafts and the magnitude of receptor signaling. The significant correlation between the expression of other genes (PTCHD1, FXYD6, and KCNIP3) and that of RGMA, may reflect their critical function in the brain (21, 26, 41). These findings raise the question of whether, in response to opioid stimulation in brain, there is crosstalk between RGMA and GRIN1, and possibly KCNIP3, FXYD6 and PTCHD1 as well.
