Heterologous Regulation of Mu-Opioid (MOP) Receptor Mobility in the Membrane of SH-SY5Y Cells

Carayon, Kévin; Moulédous, Lionel; Combedazou, Anne; Mazères, Serge; Haanappel, E.; Salomé, Laurence; Mollereau, Catherine

doi:10.1074/jbc.m114.588558

Cited by 19 publications

(9 citation statements)

References 78 publications

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“…Whether agonists change receptor mobility is controversial, but most recent studies find no or very little effect. The reported diffusion coefficients vary, but on average they are on the order of 0.1 mm 2 ×s 21 (Suzuki et al, 2005;Hern et al, 2010;Calebiro et al, 2013), although more rapid diffusion speeds have also been measured, particularly in photobleaching experiments (Henis et al, 1982;Carayon et al, 2014).…”

Section: Spatial Aspects-receptor Localization and Spatial Signaling mentioning

confidence: 99%

Spatial and Temporal Aspects of Signaling by G-Protein–Coupled Receptors

Lohse

Hofmann

2015

Mol Pharmacol

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Signaling by G-protein-coupled receptors is often considered a uniform process, whereby a homogeneously activated proportion of randomly distributed receptors are activated under equilibrium conditions and produce homogeneous, steady-state intracellular signals. While this may be the case in some biologic systems, the example of rhodopsin with its strictly local singlequantum mode of function shows that homogeneity in space and time cannot be a general property of G-protein-coupled systems. Recent work has now revealed many other systems where such simplicity does not prevail. Instead, a plethora of mechanisms allows much more complex patterns of receptor activation and signaling: different mechanisms of proteinprotein interaction; temporal changes under nonequilibrium conditions; localized receptor activation; and localized second messenger generation and degradation-all of which shape receptor-generated signals and permit the creation of multiple signal types. Here, we review the evidence for such pleiotropic receptor signaling in space and time.

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Section: Spatial Aspects-receptor Localization and Spatial Signaling mentioning

confidence: 99%

Spatial and Temporal Aspects of Signaling by G-Protein–Coupled Receptors

Lohse

Hofmann

2015

Mol Pharmacol

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“…Additionally, beta-arrestin binding, desensitization and internalization of the MOR have been heavily studied as these processes likely underlie the reduced efficacy of MOR agonists with prolonged exposure 1 . Recently, imaging-based studies of directly labeled MORs have provided an alternative to effector-dependent assays and have been used to examine MOR mobility 2–8 and subcellular localization 4,9–12 . Studies of MOR mobility utilizing fluorescence recovery after photobleaching (FRAP) and fluorescence correlation spectroscopy (FCS) have shown that MORs can exist in a variety of mobility states on the membrane even under non-stimulated conditions as the MOR can exist in nanodomains with varying lipid content and protein density or be outside of discrete nanodomains 12,13 .…”

Section: Introductionmentioning

confidence: 99%

“…The mobility of GPCRs including MORs is regulated by agonist binding and several lines of evidence suggest that distinct signaling states occurring upon agonist binding may be correlated with select mobility states 2,8,12,14–17 . Further, for the MOR, it appears that changes in lateral diffusion within the plasma membrane likely reflect interactions with different membrane proteins 3,4 .…”

Section: Introductionmentioning

confidence: 99%

Temporal dependence of shifts in mu opioid receptor mobility at the cell surface after agonist binding observed by single-particle tracking

Metz

Pennock

Krapf

et al. 2019

Sci Rep

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Agonist binding to the mu opioid receptor (MOR) results in conformational changes that allow recruitment of G-proteins, activation of downstream effectors and eventual desensitization and internalization, all of which could affect receptor mobility. The present study employed single particle tracking (SPT) of quantum dot labeled FLAG-tagged MORs to examine shifts in MOR mobility after agonist binding. FLAG-MORs on the plasma membrane were in both mobile and immobile states under basal conditions. Activation of FLAG-MORs with DAMGO caused an acute increase in the fraction of mobile MORs, and free portions of mobile tracks were partially dependent on interactions with G-proteins. In contrast, 10-minute exposure to DAMGO or morphine increased the fraction of immobile FLAG-MORs. While the decrease in mobility with prolonged DAMGO exposure corresponded to an increase in colocalization with clathrin, the increase in colocalization was present in both mobile and immobile FLAG-MORs. Thus, no single mobility state of the receptor accounted for colocalization with clathrin. These findings demonstrate that SPT can be used to track agonist-dependent changes in MOR mobility over time, but that the mobility states observed likely arise from a diverse set of interactions and will be most informative when examined in concert with particular downstream effectors.

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“…Different studies show that opioid receptors can form monomers, dimers and even higher order oligomers . Moreover, lateral dynamics of opioid receptors in the plasma membrane is complex, and can be affected by a number of factors including plasma membrane lipid composition, stimulation with specific ligands and heterologous activation of other GPCRs . While details are still debated, these studies suggest that opioid receptors may have intricate spatiotemporal signaling profiles .…”

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confidence: 99%

Dynamic lateral organization of opioid receptors (kappa, mu_wt and mu_N40D) in the plasma membrane at the nanoscale level

Rogacki

Golfetto

Tobin

et al. 2018

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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.

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Heterologous Regulation of Mu-Opioid (MOP) Receptor Mobility in the Membrane of SH-SY5Y Cells

Cited by 19 publications

References 78 publications

Spatial and Temporal Aspects of Signaling by G-Protein–Coupled Receptors

Spatial and Temporal Aspects of Signaling by G-Protein–Coupled Receptors

Temporal dependence of shifts in mu opioid receptor mobility at the cell surface after agonist binding observed by single-particle tracking

Dynamic lateral organization of opioid receptors (kappa, mu_wt and mu_N40D) in the plasma membrane at the nanoscale level

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Heterologous Regulation of Mu-Opioid (MOP) Receptor Mobility in the Membrane of SH-SY5Y Cells

Cited by 19 publications

References 78 publications

Spatial and Temporal Aspects of Signaling by G-Protein–Coupled Receptors

Spatial and Temporal Aspects of Signaling by G-Protein–Coupled Receptors

Temporal dependence of shifts in mu opioid receptor mobility at the cell surface after agonist binding observed by single-particle tracking

Dynamic lateral organization of opioid receptors (kappa, muwt and muN40D) in the plasma membrane at the nanoscale level

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Dynamic lateral organization of opioid receptors (kappa, mu_wt and mu_N40D) in the plasma membrane at the nanoscale level