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Kir3 channels undergo arrestin-dependant internalization following delta opioid receptor activation

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Abstract

Kir3 channels control excitability in the nervous system and the heart. Their surface expression is strictly regulated, but mechanisms responsible for channel removal from the membrane remain incompletely understood. Using transfected cells, we show that Kir3.1/3.2 channels and delta opioid receptors (DORs) associate in a complex which persists during receptor activation, behaving as a scaffold that allows beta-arrestin (βarr) to interact with both signaling partners. This organization favored co-internalization of DORs and Kir3 channels in a βarr-dependent manner via a clathrin/dynamin-mediated endocytic path. Taken together, these findings identify a new way of modulating Kir3 channel availability at the membrane and assign a putatively novel role for βarrs in regulating canonical effectors for G protein-coupled receptors.

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Acknowledgments

This work was supported by grant [311997] from the Natural Sciences and Engineering Research Council of Canada (NSERC) to GP. KN holds a studentship from Ste-Justine Hospital Research Center and the Faculty of Graduate and Postdoctoral Studies, University of Montreal. IC holds an FRQS fellowship.

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Authors and Affiliations

  1. Sainte-Justine Hospital Research Center, 3175 Cote Ste-Catherine, Montreal, QC, H3T 1C5, Canada

    Karim Nagi, Iness Charfi & Graciela Pineyro

  2. Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, QC, H3T 1J4, Canada

    Karim Nagi, Iness Charfi & Graciela Pineyro

  3. Department of Psychiatry, Faculty of Medicine, University of Montreal, Montreal, QC, H3T 1J4, Canada

    Graciela Pineyro

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  1. Karim Nagi
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  2. Iness Charfi
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Correspondence to Graciela Pineyro.

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Nagi, K., Charfi, I. & Pineyro, G. Kir3 channels undergo arrestin-dependant internalization following delta opioid receptor activation. Cell. Mol. Life Sci. 72, 3543–3557 (2015). https://doi.org/10.1007/s00018-015-1899-x

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