Signaling-Biased and Constitutively Active Dopamine D2 Receptor Variant.

ABSTRACT: A dopamine D2 receptor mutation was recently identified in a family with a novel hyperkinetic movement disorder. Compared to the wild type D2 receptor, the novel allelic variant D2-I²¹²F activates a Gα_i1β₁γ₂ heterotrimer with higher potency and modestly enhanced basal activity in human embryonic kidney (HEK) 293 cells and has decreased capacity to recruit arrestin3. We now report that omitting overexpressed G protein-coupled receptor kinase-2 (GRK2) decreased the potency and efficacy of quinpirole for arrestin recruitment. The relative efficacy of quinpirole for arrestin recruitment to D2-I²¹²F compared to D2-WT was considerably lower without overexpressed GRK2 than with added GRK2. D2-I²¹²F exhibited higher basal activation

SUBMITTER: Rodriguez-Contreras D 

PROVIDER: S-EPMC8528033 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature