4.4 Article

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

期刊

TRAFFIC
卷 19, 期 9, 页码 690-709

出版社

WILEY
DOI: 10.1111/tra.12582

关键词

dynamic lateral organization; fluorescence correlation spectroscopy; GPCR; nanoscopy; opioid receptor; pair-correlation photoactivated localization microscopy; super-resolution

资金

  1. Foundation for Strategic Research [SBE13 -0115]
  2. Foundation Olle Engkvist Byggmastare
  3. Irell & Manella Graduate School of Biological Sciences at City of Hope
  4. National Institutes of Health [R21 CA174608]
  5. Eugene and Ruth Roberts Summer Student Academy
  6. Beckman Research Institute of the City of Hope
  7. Knut and Alice Wallenberg Foundation [KAW2011.0218]
  8. Swedish Research Council [VR 2012-2595]
  9. Swedish Foundation for Strategic Research (SSF) [SBE13-0115] Funding Source: Swedish Foundation for Strategic Research (SSF)

向作者/读者索取更多资源

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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