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GRK mediates μ-opioid receptor plasma membrane reorganization

Gondin, Arisbel B.; Halls, Michelle L.; Canals, Meritxell; Briddon, Stephen J.

Authors

Arisbel B. Gondin

Michelle L. Halls



Abstract

Differential regulation of the μ-opioid receptor (MOP) has been linked to the development of opioid tolerance and dependence which both limit the clinical use of opioid analgesics. At a cellular level, MOP regulation occurs via receptor phosphorylation, desensitization, plasma membrane redistribution, and internalization. Here, we used fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP) to detect and quantify ligand-dependent changes in the plasma membrane organization of MOP expressed in human embryonic kidney (HEK293) cells. The low internalizing agonist morphine and the antagonist naloxone did not alter constitutive MOP plasma membrane organization. In contrast, the internalizing agonist DAMGO changed MOP plasma membrane organization in a pertussis toxin-insensitive manner and by two mechanisms. Firstly, it slowed MOP diffusion in a manner that was independent of internalization but dependent on GRK2/3. Secondly, DAMGO reduced the surface receptor number and the proportion of mobile receptors, and increased receptor clustering in a manner that was dependent on clathrin-mediated endocytosis. Overall, these results suggest the existence of distinct sequential MOP reorganization events at the plasma membrane and provide insights into the specific protein interactions that control MOP plasma membrane organization.

Journal Article Type Article
Publication Date May 1, 2019
Journal Frontiers in Molecular Neuroscience
Electronic ISSN 1662-5099
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 12
APA6 Citation Gondin, A. B., Halls, M. L., Canals, M., & Briddon, S. J. (2019). GRK mediates μ-opioid receptor plasma membrane reorganization. Frontiers in Molecular Neuroscience, 12, https://doi.org/10.3389/fnmol.2019.00104
DOI https://doi.org/10.3389/fnmol.2019.00104
Keywords Molecular Biology; Cellular and Molecular Neuroscience
Publisher URL https://www.frontiersin.org/articles/10.3389/fnmol.2019.00104/full

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