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

被引：19

作者：

Rogacki, Maciej K. ^{[1
,6
]}

Golfetto, Ottavia ^{[2
]}

Tobin, Steven J. ^{[2
]}

Li, Tianyi ^{[1
]}

Biswas, Sunetra ^{[2
]}

Jorand, Raphael ^{[2
]}

Zhang, Huiying ^{[2
]}

Radoi, Vlad ^{[1
]}

Ming, Yu ^{[1
]}

Svenningsson, Per ^{[1
]}

Ganjali, Daniel ^{[3
]}

Wakefield, Devin L. ^{[2
]}

Sideris, Athanasios ^{[3
]}

Small, Alexander R. ^{[4
]}

Terenius, Lars ^{[1
,5
]}

Jovanovic-Talisman, Tijana ^{[2
]}

Vukojevic, Vladana ^{[1
]}

机构：

[1] Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, CMM L8 01, S-17176 Stockholm, Sweden

[2] City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Med, Duarte, CA 91010 USA

[3] Univ Calif Irvine, Henry Samueli Sch Engn, Dept Mech & Aerosp Engn, Irvine, CA USA

[4] Calif State Polytech Univ Pomona, Dept Phys & Astron, Pomona, CA 91768 USA

[5] Scripps Res Inst, Dept Mol & Cellular Neurosci, La Jolla, CA 92037 USA

[6] Univ Antwerp, Dept Pharmaceut Sci, Med Chem, B-2610 Antwerp, Belgium

来源：

TRAFFIC | 2018年 / 19卷 / 09期

基金：

美国国家卫生研究院; 瑞典研究理事会;

关键词：

dynamic lateral organization; fluorescence correlation spectroscopy; GPCR; nanoscopy; opioid receptor; pair-correlation photoactivated localization microscopy; super-resolution; FLUORESCENCE CORRELATION SPECTROSCOPY; PROTEIN-COUPLED RECEPTOR; SINGLE-NUCLEOTIDE POLYMORPHISM; CROSS-CORRELATION SPECTROSCOPY; RESONANCE ENERGY-TRANSFER; PAIR CORRELATION-ANALYSIS; CHOLERA-TOXIN BINDING; LIPID RAFTS; CELL-SURFACE; SH-SY5Y CELLS;

D O I：

10.1111/tra.12582

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：690 / 709

页数：20