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Mol Biol Cell. 2017 Aug 1;28(16):2202-2219. doi: 10.1091/mbc.E17-01-0030. Epub 2017 May 31.

PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network.

Author information

1
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.
2
Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA 15213.
3
Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213.
4
Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213.
5
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213 map3@andrew.cmu.edu.

Abstract

The interplay between signaling and trafficking by G protein-coupled receptors (GPCRs) has focused mainly on endocytic trafficking. Whether and how surface delivery of newly synthesized GPCRs is regulated by extracellular signals is less understood. Here we define a signaling-regulated checkpoint at the trans-Golgi network (TGN) that controls the surface delivery of the delta opioid receptor (δR). In PC12 cells, inhibition of phosphoinositide-3 kinase (PI3K) activity blocked export of newly synthesized δR from the Golgi and delivery to the cell surface, similar to treatment with nerve growth factor (NGF). Depletion of class II phosphoinositide-3 kinase α (PI3K C2A), but not inhibition of class I PI3K, blocked δR export to comparable levels and attenuated δR-mediated cAMP inhibition. NGF treatment displaced PI3K C2A from the Golgi and optogenetic recruitment of the PI3K C2A kinase domain to the TGN-induced δR export downstream of NGF. Of importance, PI3K C2A expression promotes export of endogenous δR in primary trigeminal ganglion neurons. Taken together, our results identify PI3K C2A as being required and sufficient for δR export and surface delivery in neuronal cells and suggest that it could be a key modulator of a novel Golgi export checkpoint that coordinates GPCR delivery to the surface.

PMID:
28566554
PMCID:
PMC5531736
DOI:
10.1091/mbc.E17-01-0030
[Indexed for MEDLINE]
Free PMC Article

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