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Gβ5 recruits R7 RGS proteins to GIRK channels to regulate the timing of neuronal inhibitory signaling

Abstract

The type 5 G protein β subunit (Gβ5) can form complexes with members of the regulator of G protein signaling 7 (RGS7) family, but its relevance to neuronal G protein signaling is unclear. We found that mouse RGS7-Gβ5 complexes bound to G protein–gated potassium channels and facilitated their functional coupling to GABAB receptors in neurons. Our findings identify a compartmentalization mechanism that is critical for ensuring high temporal resolution of neuronal G protein signaling.

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Figure 1: The Gβ5–RGS7 complex binds specifically to GIRK channels.
Figure 2: Gβ5 ablation delays GABAB-GIRK signaling kinetics.
Figure 3: Gβ5 ablation potentiates GABAB-dependent behavior.

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Acknowledgements

We thank J. Chen for providing the Gβ5−/− mice, W. Simonds for the gift of antibodies to Gβ5 and RGS7 and M. Parent for assistance with the hippocampal slicing technique. This work was supported by US National Institutes of Health grants DA021743 (K.A.M.), DA026405 (K.A.M.), EY018139 (K.A.M.), MH061933 (K.W.), DA011806 (K.W.), DA019666 (M.J.T.) and MH078291 (J.C.-S.), a McKnight Land-Grant Award (K.A.M), and an award from the Whitehall Foundation (M.J.T.).

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K.W., K.A.M., S.K. and M.J.T. designed the experiments, analyzed the data and wrote the manuscript. K.X., K.L.A., S.K., J.C.-S. and K.W. conducted the experiments.

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Correspondence to Kevin Wickman or Kirill A Martemyanov.

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The authors declare no competing financial interests.

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Xie, K., Allen, K., Kourrich, S. et al. Gβ5 recruits R7 RGS proteins to GIRK channels to regulate the timing of neuronal inhibitory signaling. Nat Neurosci 13, 661–663 (2010). https://doi.org/10.1038/nn.2549

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