A Genetically Encoded Biosensor Reveals Location Bias of Opioid Drug Action.

TitleA Genetically Encoded Biosensor Reveals Location Bias of Opioid Drug Action.
Publication TypeJournal Article
Year of Publication2018
AuthorsStoeber, M., D. JulliƩ, B. T. Lobingier, T. Laeremans, J. Steyaert, P. W. Schiller, A. Manglik, and M. von Zastrow
Date Published2018 Jun 06

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.

Alternate JournalNeuron
PubMed ID29754753
Grant ListR01 DA004443 / DA / NIDA NIH HHS / United States
Research group: