Publication
Title
Dynamic lateral organization of opioid receptors (kappa, $mu_{wt}$ and $mu_{N40D}$) in the plasma membrane at the nanoscale level
Author
Abstract
 Opioid receptors are important pharmacological targets for the management of numerous medical conditions (eg, severe pain), but they are also the gateway to the development of deleterious side effects (eg, opiate addiction). Opioid receptor signaling cascades are well characterized. However, quantitative information regarding their lateral dynamics and nanoscale organization in the plasma membrane remains limited. Since these dynamic properties are important determinants of receptor function, it is crucial to define them. Herein, the nanoscale lateral dynamics and spatial organization of kappa opioid receptor (KOP), wild type mu opioid receptor (MOPwt), and its naturally occurring isoform (MOPN40D) were quantitatively characterized using fluorescence correlation spectroscopy and photoactivated localization microscopy. Obtained results, supported by ensemble-averaged Monte Carlo simulations, indicate that these opioid receptors dynamically partition into different domains. In particular, significant exclusion from GM1 ganglioside-enriched domains and partial association with cholesterol-enriched domains was observed. Nanodomain size, receptor population density and the fraction of receptors residing outside of nanodomains were receptor-specific. KOP-containing domains were the largest and most densely populated, with the smallest fraction of molecules residing outside of nanodomains. The opposite was true for MOPN40D. Moreover, cholesterol depletion dynamically regulated the partitioning of KOP and MOPwt, whereas this effect was not observed for MOPN40D.
Language
English
Source (journal)
Traffic. - Place of publication unknown
Publication
Place of publication unknown : 2018
ISSN
1398-9219
Volume/pages
19 :9 (2018) , p. 690-709
ISI
000441759600004
Pubmed ID
29808515
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
 Faculty/Department Research group Publication type Subject Affiliation Publications with a UAntwerp address