Palmitoylation and Membrane Cholesterol Stabilize mu-Opioid Receptor Homodimerization and G Protein Coupling

doi:10.1186/1471-2121-13-6

CSpace

	Palmitoylation and Membrane Cholesterol Stabilize mu-Opioid Receptor Homodimerization and G Protein Coupling
	Hui Zheng; Elizabeth A Pearsall; Dow P Hurst; Yuhan Zhang; Ji Chu; Yali Zhou; Patricia H Reggio; Horace H Loh; Ping-Yee Law
	2012
Source Publication	BMC Cell Biology
Volume	13 Issue:1 Pages:6
Abstract	Background A 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. Results C3.55(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. Conclusions We 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.
Keyword	Palmitoylation Cholesterol Homodimerization g Protein Coupling
DOI	10.1186/1471-2121-13-6
URL	查看原文
Indexed By	SCI
Citation statistics
Document Type	期刊论文
Identifier	http://ir.foo.ac.cn/handle/2SETSVCV/617
Collection	中国科学院广州生物医药与健康研究院
Recommended Citation GB/T 7714	Hui Zheng,Elizabeth A Pearsall,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	Hui Zheng.,Elizabeth A Pearsall.,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	Hui Zheng,et al."Palmitoylation and Membrane Cholesterol Stabilize mu-Opioid Receptor Homodimerization and G Protein Coupling".BMC Cell Biology 13.1(2012):6.

Files in This Item:		Download All
File Name/Size	DocType	Version	Access	License
Palmitoylation and m（5414KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	View Download

File name:	Palmitoylation and membrane cholesterol stabilize μ-opioid receptor homodimerization and G protein coupling.pdf
Format:	Adobe PDF

If you have any objections to this item, please fill out the form below and the administrator will contact you as soon as possible.
Content:
Email：	*
Institution:
Verification Code:	Refresh

Any comments and suggestions are welcomed.
Title:	*
Content:
Email：	*
Verification Code:	Refresh

中国科学院广州生物医药与健康研究院机构知识库

Background

Results

Conclusions