Palmitoylation and Membrane Cholesterol Stabilize mu-Opioid Receptor Homodimerization and G Protein Coupling
文献类型：期刊论文
| 作者 | Elizabeth A Pearsall; Hui Zheng; Dow P Hurst; Yuhan Zhang; Ji Chu; Yali Zhou; Patricia H Reggio; Horace H Loh; Ping-Yee Law |
| 刊名 | BMC Cell Biology
 |
| 出版日期 | 2012 |
| 卷号 | 13期号:1页码:6 |
| 关键词 | Palmitoylation Cholesterol Homodimerization g Protein Coupling |
| DOI | 10.1186/1471-2121-13-6 |
| 英文摘要 | BackgroundA cholesterol-palmitoyl interaction has been reported to occur in the dimeric interface of the β2-adrenergic receptor crystal structure. We sought to investigate whether a similar phenomenon could be observed with μ-opioid receptor (OPRM1), and if so, to assess the role of cholesterol in this class of G protein-coupled receptor (GPCR) signaling. ResultsC3.55(170) was determined to be the palmitoylation site of OPRM1. Mutation of this Cys to Ala did not affect the binding of agonists, but attenuated receptor signaling and decreased cholesterol associated with the receptor signaling complex. In addition, both attenuation of receptor palmitoylation (by mutation of C3.55[170] to Ala) and inhibition of cholesterol synthesis (by treating the cells with simvastatin, a HMG-CoA reductase inhibitor) impaired receptor signaling, possibly by decreasing receptor homodimerization and Gαi2 coupling; this was demonstrated by co-immunoprecipitation, immunofluorescence colocalization and fluorescence resonance energy transfer (FRET) analyses. A computational model of the OPRM1 homodimer structure indicated that a specific cholesterol-palmitoyl interaction can facilitate OPRM1 homodimerization at the TMH4-TMH4 interface. ConclusionsWe demonstrate that C3.55(170) is the palmitoylation site of OPRM1 and identify a cholesterol-palmitoyl interaction in the OPRM1 complex. Our findings suggest that this interaction contributes to OPRM1 signaling by facilitating receptor homodimerization and G protein coupling. This conclusion is supported by computational modeling of the OPRM1 homodimer. |
| URL标识 | 查看原文 |
| 源URL | [http://ir.foo.ac.cn/handle/2SETSVCV/617]  |
| 专题 | 中国科学院广州生物医药与健康研究院 |
| 推荐引用方式 GB/T 7714 | Elizabeth A Pearsall,Hui Zheng,Dow P Hurst,et al. Palmitoylation and Membrane Cholesterol Stabilize mu-Opioid Receptor Homodimerization and G Protein Coupling[J]. BMC Cell Biology,2012,13(1):6. |
| APA | Elizabeth A Pearsall.,Hui Zheng.,Dow P Hurst.,Yuhan Zhang.,Ji Chu.,...&Ping-Yee Law.(2012).Palmitoylation and Membrane Cholesterol Stabilize mu-Opioid Receptor Homodimerization and G Protein Coupling.BMC Cell Biology,13(1),6. |
| MLA | Elizabeth A Pearsall,et al."Palmitoylation and Membrane Cholesterol Stabilize mu-Opioid Receptor Homodimerization and G Protein Coupling".BMC Cell Biology 13.1(2012):6. |
入库方式： OAI收割
来源：广州生物医药与健康研究院
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