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

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...

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Detalles Bibliográficos
Autores principales: Shiwarski, Daniel J., Darr, Marlena, Telmer, Cheryl A., Bruchez, Marcel P., Puthenveedu, Manojkumar A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531736/
https://www.ncbi.nlm.nih.gov/pubmed/28566554
http://dx.doi.org/10.1091/mbc.E17-01-0030
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author Shiwarski, Daniel J.
Darr, Marlena
Telmer, Cheryl A.
Bruchez, Marcel P.
Puthenveedu, Manojkumar A.
author_facet Shiwarski, Daniel J.
Darr, Marlena
Telmer, Cheryl A.
Bruchez, Marcel P.
Puthenveedu, Manojkumar A.
author_sort Shiwarski, Daniel J.
collection PubMed
description 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.
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spelling pubmed-55317362017-10-16 PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network Shiwarski, Daniel J. Darr, Marlena Telmer, Cheryl A. Bruchez, Marcel P. Puthenveedu, Manojkumar A. Mol Biol Cell Articles 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. The American Society for Cell Biology 2017-08-01 /pmc/articles/PMC5531736/ /pubmed/28566554 http://dx.doi.org/10.1091/mbc.E17-01-0030 Text en © 2017 Shiwarski et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Shiwarski, Daniel J.
Darr, Marlena
Telmer, Cheryl A.
Bruchez, Marcel P.
Puthenveedu, Manojkumar A.
PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network
title PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network
title_full PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network
title_fullStr PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network
title_full_unstemmed PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network
title_short PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network
title_sort pi3k class ii α regulates δ-opioid receptor export from the trans-golgi network
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531736/
https://www.ncbi.nlm.nih.gov/pubmed/28566554
http://dx.doi.org/10.1091/mbc.E17-01-0030
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