The dynamic organization of G protein-coupled receptors in the plasma membrane is suspected of playing a role in their function. The regulation of the diffusion mode of the mu-opioid (MOP) receptor was previously shown to be agonist-specific. Here we investigate the regulation of MOP receptor diffusion by heterologous activation of other G protein-coupled receptors and characterize the dynamic properties of the MOP receptor within the heterodimer MOP/neuropeptide FF (NPFF2) receptor. The data show that the dynamics and signaling of the MOP receptor in SH-SY5Y cells are modified by the activation of α2-adrenergic and NPFF2 receptors, but not by the activation of receptors not described to interact with the opioid receptor. By combining, for the first time, fluorescence recovery after photobleaching at variable radius experiments with bimolecular fluorescence complementation, we show that the MOP/NPFF2 heterodimer adopts a specific diffusion behavior that corresponds to a mix of the dynamic properties of both MOP and NPFF2 receptors. Altogether, the data suggest that heterologous regulation is accompanied by a specific organization of receptors in the membrane.
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http://dx.doi.org/10.1074/jbc.M114.588558 | DOI Listing |
Alcohol Clin Exp Res (Hoboken)
December 2024
Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.
Background: Adolescent alcohol use is the norm, but only some develop a substance use disorder. The increased risk might reflect heightened mesocorticolimbic responses to reward-related cues but results published to date have been inconsistent.
Methods: Young social drinkers (age 18.
Commun Biol
December 2024
Robarts Research Institute, University of Western Ontario, London, ON, N6A 5B7, Canada.
The Pro/N-degron recognizing C-terminal to LisH (CTLH) complex is an E3 ligase of emerging interest in the developmental biology field and for targeted protein degradation (TPD) modalities. The human CTLH complex forms distinct supramolecular ring-shaped structures dependent on the multimerization of WDR26 or muskelin β-propeller proteins. Here, we find that, in HeLa cells, CTLH complex E3 ligase activity is dictated by an interplay between WDR26 and muskelin in tandem with muskelin autoregulation.
View Article and Find Full Text PDFBiochem Pharmacol
November 2024
Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland. Electronic address:
The antinociceptive effect of the opioid drugs is achieved through activation of the µ-opioid receptor (MOP). The orthosteric and allosteric sites of opioid receptors may be modulated, orthosteric site by endogenous i.e.
View Article and Find Full Text PDFNeuropsychopharmacol Rep
March 2025
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Although methamphetamine (METH) and other addictive substance use disorders are a major social problem worldwide, appropriate pharmacotherapies have not yet been discovered. Subtype-nonselective opioid receptor antagonists, such as naltrexone (NTX), have been reported to suppress METH addiction, but unclear are the opioid receptor subtypes that are involved in this beneficial effect. To clarify the role of μ-opioid receptors (MOPs), we examined effects of the novel nonpeptidic MOP-selective antagonist UD-030 on the acquisition and expression of METH-induced conditioned place preference (CPP) using behavioral tests in C57BL/6J mice.
View Article and Find Full Text PDFTransl Psychiatry
November 2024
Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, SE-17176, Sweden.
Naltrexone (NTX), a homolog of the opiate antidote naloxone, is an orally active long-acting general opioid receptor antagonist used in the treatment of opiate dependence. NTX is also found to relieve craving for alcohol and is one of few FDA-approved medications for treatment of alcohol use disorder (AUD). While it was early on established that NTX acts by blocking the binding of endogenous opioid peptide ligands released by alcohol, experimental evidence emerged that could not be fully accounted for by this explanation alone, suggesting that NTX may have additional modes of action.
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