Dopamine D2L receptor-interacting proteins regulate dopaminergic signaling

Norifumi Shioda

doi:10.1016/j.jphs.2017.10.002

Dopamine D_2L receptor-interacting proteins regulate dopaminergic signaling

J Pharmacol Sci. 2017 Oct 14:S1347-8613(17)30171-8. doi: 10.1016/j.jphs.2017.10.002. Online ahead of print.

Author

Norifumi Shioda¹

Affiliation

¹ Department of Biofunctional Analysis, Laboratory of Molecular Biology, Gifu Pharmaceutical University, Gifu 501-1196, Japan. Electronic address: shioda@gifu-pu.ac.jp.

PMID: 29107444
DOI: 10.1016/j.jphs.2017.10.002

Abstract

Dopamine receptor family proteins include seven transmembrane and trimeric GTP-binding protein-coupled receptors (GPCRs). Among them, the dopamine D₂ receptor (D₂R) is most extensively studied. All clinically used antipsychotic drugs serve as D₂R antagonists in the mesolimbic dopamine system, and their ability to block D₂R signaling is positively correlated with antipsychotic efficiency. Human genetic studies also show a significant association of DRD2 polymorphisms with disorders including schizophrenia and Parkinson's disease. D₂R exists as two alternatively spliced isoforms, the long isoform (D_2LR) and the short isoform (D_2SR), which differ in a 29-amino acid (AA) insert in the third cytoplasmic loop. Importantly, previous reports demonstrate functional diversity between the two isoforms in humans. In this review, we focus on binding proteins that specifically interact with the D_2LR 29AA insert. We discuss how D₂R activities are mediated not only by heterotrimeric G proteins but by D_2LR-interacting proteins, which in part regulate diverse D₂R activities.

Keywords: Alternatively spliced isoforms; Antipsychotic drugs; D(2L)R-interacting proteins; DRD2 polymorphisms; Dopamine D(2L) receptor.

Publication types

Review