G protein-gated inwardly rectifying potassium (GIRK) channels play an important 
role in regulating neuronal excitability. Sorting nexin 27b (SNX27b), which 
reduces surface expression of GIRK channels through a PDZ domain interaction, 
contains a putative Ras-association (RA) domain with unknown function. Deleting 
the RA domain in SNX27b (SNX27b-ΔRA) prevents the down-regulation of 
GIRK2c/GIRK3 channels. Similarly, a point mutation (K305A) in the RA domain 
disrupts regulation of GIRK2c/GIRK3 channels and reduces H-Ras binding in vitro. 
Finally, the dominant-negative H-Ras (S17N) occludes the SNX27b-dependent 
decrease in surface expression of GIRK2c/GIRK3 channels. Thus, the presence of a 
functional RA domain and the interaction with Ras-like G proteins comprise a 
novel mechanism for modulating SNX27b control of GIRK channel surface expression 
and cellular excitability.