Figure 1. Deletion of RA domain in SNX27b impairs functional regulation of GIRK channels.

A, Cartoon shows model of GIRK channels regulation by SNX27b. GIRK channels recycle through endosomal compartments. SNX27b associating with GIRK2c/3 channels in the early endosome (EE) reduces plasma membrane expression (PM) by targeting some channels to the late endosome (LE). B, SNX27 contains three functional domains; PDZ, PX and RA. GIRK2c and GIRK3 contain a C-terminal PDZ binding motif (-E(S/N)ESKV). C, Examples of baclofen-induced (100 µM) and Ba²⁺-sensitive (1 mM Ba²⁺) currents in HEK293T cells transfected with cDNA for GABA_B1a/B2 receptors, GIRK2c/GIRK3 and either control vector, SNX27b or SNX27b-ΔRA. Agonist-independent basal currents are revealed by inhibition with 1 mM Ba²⁺. D, Average baclofen-induced current densities (I_Baclofen) for control (–41.3±5.2 pA⋅pF⁻¹, n = 8), SNX27b (–11.0±3.6 pA⋅pF⁻¹, n = 8) and SNX27b- ΔRA (–55.9±8.2 pA⋅pF⁻¹, n = 13) with GIRK2c/GIRK3. E, Average I_Baclofen for control (–15.7±3.6 pA⋅pF⁻¹, n = 6) and SNX27b-ΔRA (–18.6±4.9 pA⋅pF⁻¹, n = 5) with GIRK1/GIRK3 (**P<0.05, one way ANOVA followed by Bonferroni post hoc test; n.s. – not significant).