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Gb5‐RGS complexes gate adenylyl cyclase sensitization and control neuronal excitability
Author(s) -
Xie Keqiang,
Kourrich Saïd,
Ge Shencheng,
Collins Victoria E.,
Haynes Christy L.,
Renner Kenneth J.,
Meisel Robert L.,
Lujan Rafael,
Martemyanov Kirill A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.803.4
Complexes of the atypical type 5 G protein beta subunit (Gb5) with members of the R7 family of Regulator of G protein Signaling (R7 RGS) critically shape a range of the fundamental processes mediated by G protein signaling in the nervous system. However, the molecular mechanisms of Gb5‐RGS underlying the regulation of specific signaling is unclear. We show here that mice lacking Gb5‐RGS develop severe motor coordination deficit, pronounced locomotion hyperactivity and enhanced responsiveness of a number of pre‐ and postsynaptic G protein coupled receptors. Gb5‐RGS gates adenylyl cyclase activity in neuronal system and loss of Gb5‐RGS results in the sensitization of adenylyl cyclase which in turn triggers activation of cAMP‐PKA signaling, leading to pronounced hyperactivity deficiency in inhibitory GABA(A) signaling. In conclusion, these results establish Gb5‐RGS complexes as key players that gate cAMP signaling and control neuronal excitability.