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

Daniel J Shiwarski1,2, Marlena Darr1, Cheryl A Telmer1

  • 1Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.

Molecular Biology of the Cell
|June 2, 2017
PubMed

Insights

This study reveals a novel Golgi checkpoint regulating the surface delivery of delta opioid receptors (δR). Phosphoinositide-3 kinase C2 alpha (PI3K C2A) is crucial for this process in neuronal cells.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Molecular Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) signaling and trafficking are primarily studied via endocytosis.
  • Regulation of newly synthesized GPCRs' surface delivery by extracellular signals remains largely unknown.

Purpose of the Study:

  • To investigate the regulation of delta opioid receptor (δR) surface delivery by extracellular signals.
  • To identify signaling pathways controlling GPCR export from the Golgi.

Main Methods:

  • Utilized PC12 cells and primary trigeminal ganglion neurons.
  • Employed phosphoinositide-3 kinase (PI3K) inhibition and depletion (PI3K C2A).
  • Used nerve growth factor (NGF) treatment and optogenetics for pathway manipulation.

Main Results:

  • Inhibition of PI3K blocked δR export from the Golgi to the cell surface.
  • Depletion of PI3K C2A, but not class I PI3K, inhibited δR export and attenuated receptor function.
  • NGF treatment displaced PI3K C2A; optogenetic recruitment induced δR export.
  • PI3K C2A expression promoted endogenous δR export in neurons.

Conclusions:

  • PI3K C2A is essential and sufficient for δR export and surface delivery in neuronal cells.
  • Identified a novel Golgi export checkpoint regulated by PI3K C2A.
  • Suggests PI3K C2A coordinates GPCR surface delivery via a new Golgi export mechanism.

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