Xian-Yu Liu

My interests focus on the physiological relevance of protein-protein interactions including opioid receptors, bombesin receptors, serotonin receptors, tachykinin receptors, dopamine receptors and glutamate receptors. I developed an interest in protein-protein interaction during my postdoctoral training in the University of Missouri - Kansas City. I studied dopamine-glutamate interactions in rat neostriatum upon cocaine stimulation. I found that cocaine enhanced physical interactions between dopamine receptors D2R and NMDA subunit NR2B and resulted in reduced phosphorylation level of NR2B. This type of receptors interaction might be responsible for synergistically inhibiting the D2R-mediated circuits in the basal ganglia and fulfilling the stimulative effect of cocaine. In the following study I screened D3R interacting proteins in neostriatum and examined calcium-dependent interaction between CaMKIIα and D3R. CaMKIIα binded to the N-terminal region of the third intracellular loop of D3R and transformed D3R into a biochemical substrate of the kinase. Phosphorylation of D3R at a selective serine site (S229) by CaMKIIα inhibited D3R efficacy. This is critical for integrating dopamine signaling to control behavioral sensitivity to cocaine. Then I moved on to study the role of receptor interactions in itch sensation in Washington University in St Louis. I got involved in the exciting discovery that a small group of mouse spinal neurons expressing gastrin releasing peptide receptor (GRPR), an itch specific receptor in mouse spinal cord, are responsible for itch transmission evoked by various pruritognes. Importantly, those neurons are dispensable for pain sensation. Based on that finding, I screened different splicing variants of mouse mu opioid receptors and identified MOR-1D as one of the interacting proteins associated with GRPR. MOR1D-GRPR interaction was responsible for morphine-induced activation of spinal itch pathway and scratching behavior in mouse, while MOR-1 was the receptor for morphine analgesic effect. Besides MOR1D I also found interactions between GRPR and other itch-related receptors, e.g. serotonin receptors, Mrgprs and TRP channels. I believe these ongoing studies will surely give insight into the mechanisms underlying itch sensation.