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Updated: May 12, 2026

A Fluorescent Screening Assay for Identifying Modulators of GIRK Channels
Published on: April 24, 2012
Ras-association domain of sorting Nexin 27 is critical for regulating expression of GIRK potassium channels
Bartosz Balana1, Laia Bahima, Karthik Bodhinathan
1Peptide Biology Laboratories, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
Abstract:
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.
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