PubMed 23536889

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir2.2 , Kir2.3 , Kir3.2 , Kir3.3 , Kv1.4

Title: Ras-association domain of sorting Nexin 27 is critical for regulating expression of GIRK potassium channels.

Authors: Bartosz Balana, Laia Bahima, Karthik Bodhinathan, Jaume J Taura, Natalie M Taylor, Margaret Y Nettleton, Francisco Ciruela, Paul A Slesinger

Journal, date & volume: PLoS ONE, 2013 , 8, e59800

PubMed link:

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.