title: Ras-association domain of sorting Nexin 27 is critical for regulating expression of GIRK potassium channels.
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.
authors.affiliation: Peptide Biology Laboratories, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Balana
authors.forename: Laia
authors.initials: L
authors.lastname: Bahima
authors.forename: Karthik
authors.initials: K
authors.lastname: Bodhinathan
authors.forename: Jaume J
authors.initials: JJ
authors.lastname: Taura
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Taylor
authors.forename: Margaret Y
authors.initials: MY
authors.lastname: Nettleton
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.forename: Paul A
authors.initials: PA
authors.lastname: Slesinger
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D021381:Protein Transport; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D016415:Sequence Alignment; D058305:Sorting Nexins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C094401:KCNJ6 protein, human; C522885:SNX27 protein, human; D058305:Sorting Nexins; D016283:Proto-Oncogene Proteins p21(ras)
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