en
Scientific article
Open access
English

A genetically encoded biosensor reveals location bias of opioid drug action

Published inNeuron, vol. 98, no. 5, p. 963-976.e5
Publication date2018
Abstract

Opioid receptors (ORs) precisely modulate behavior when activated by native peptide ligands but distort behaviors to produce pathology when activated by non-peptide drugs. A fundamental question is how drugs differ from peptides in their actions on target neurons. Here, we show that drugs differ in the subcellular location at which they activate ORs. We develop a genetically encoded biosensor that directly detects ligand-induced activation of ORs and uncover a real-time map of the spatiotemporal organization of OR activation in living neurons. Peptide agonists produce a characteristic activation pattern initiated in the plasma membrane and propagating to endosomes after receptor internalization. Drugs produce a different activation pattern by additionally driving OR activation in the somatic Golgi apparatus and Golgi elements extending throughout the dendritic arbor. These results establish an approach to probe the cellular basis of neuromodulation and reveal that drugs distort the spatiotemporal landscape of neuronal OR activation.

Keywords
  • Analgesics
  • Opioid/metabolism
  • Animals
  • Biosensing Techniques
  • Cell Membrane/metabolism
  • Dendrites/metabolism
  • Endosomes/metabolism
  • Enkephalin
  • Ala2 MePhe4 Gly5/metabolism
  • Enkephalin
  • D Penicillamine 2.5/metabolism
  • Enkephalin
  • Leucine2Alanine/metabolism
  • Golgi Apparatus/metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Space
  • Microscopy
  • Fluorescence
  • Morphine/metabolism
  • Naloxone
  • Narcotic Antagonists
  • Neurons/metabolism
  • Peptides/metabolism
  • Rats
  • Receptors
  • Opioid/metabolism
  • Spatio Temporal Analysis
Affiliation Not a UNIGE publication
Citation (ISO format)
STOEBER, Miriam Carolin et al. A genetically encoded biosensor reveals location bias of opioid drug action. In: Neuron, 2018, vol. 98, n° 5, p. 963–976.e5. doi: 10.1016/j.neuron.2018.04.021
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0896-6273
406views
169downloads

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