Receptor transactivation or crosstalk refers to instances in which the signaling of a given receptor is regulated by different classes of receptors. Functional crosstalk between α4β2 nicotinic acetylcholine receptor (nAChR) and D3 dopamine receptor (D3R) that belong to the family of ligand-gated ion channels and G protein-coupled receptors, respectively, has been reported from brain dopaminergic neurons. For example, D3R is involved in the development of reward-related behaviors induced by α4β2 nAChR stimulation. However, the molecular mechanisms involved in their crosstalk remain unclear. Among PKC isoforms (α, βII, γ, and δ) evaluated in this study, PKCβII interacted with D3R and potentiated D3R endocytosis. Following α4β2 nAChR stimulation, activated PKCβII translocated to the plasma membrane to induce clathrin-mediated endocytosis of D3R, resulting in downregulation and signal inhibition. Considering that D3R plays important roles in mediating reward-related physiological actions of α4β2 nAChR, this study could provide a new insight into the regulatory mechanism involved in nicotine addiction.
Keywords: Clathrin-mediated endocytosis; D(3) dopamine receptor; Downregulation; Protein kinase C; α4β2 nicotinic receptor.
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