Spatial Intensity Distribution Analysis: Studies of G Protein-Coupled Receptor Oligomerisation.
Spatial Intensity Distribution Analysis: Studies of G Protein-Coupled Receptor Oligomerisation.
复制标题
空间强度分布分析：G蛋白偶联受体低聚的研究。
DOI：
10.1016/j.tips.2017.09.001
复制
发表时间：
2018-03
影响因子：
13.8
通讯作者：
Milligan G
中科院分区：
文献类型：
--
作者：
Pediani JD;Ward RJ;Marsango S;Milligan G
Spatial intensity distribution analysis (SpIDA) is a recently developed approach for determining quaternary structure information on fluorophore-labelled proteins of interest in situ. It can be applied to live or fixed cells and native tissue. Using confocal images, SpIDA generates fluorescence intensity histograms that are analysed by super-Poissonian distribution functions to obtain density and quantal brightness values of the fluorophore-labelled protein of interest. This allows both expression level and oligomerisation state of the protein to be determined. We describe the application of SpIDA to investigate the oligomeric state of G protein-coupled receptors (GPCRs) at steady state and following cellular challenge, and consider how SpIDA may be used to explore GPCR quaternary organisation in pathophysiology and to stratify medicines. GPCRs may exist and function as monomers: however, abundant evidence suggests they can form dimers/oligomers. This concept has implications for drug discovery as it may offer opportunities to modulate the effects of known pharmaceuticals or identify new drug therapies. A variety of approaches have been applied to this issue from traditional biochemical techniques, via resonance energy transfer approaches to recently developed image analysis-based techniques such as SpIDA. This uses mathematical analysis of confocal microscopy images to generate quantal brightness and density information for a fluorophore-tagged receptor. SpIDA can be applied to live or fixed cells and native tissue. SpIDA has been applied to GPCRs from each of the major subfamilies to explore their oligomerisation status at steady state and their regulation by receptor density and ligand binding.
登录
查看更多内容
DOI：
10.1074/jbc.m116.754887
发表时间：
2016-12-30
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Alvarez-Curto E;Inoue A;Jenkins L;Raihan SZ;Prihandoko R;Tobin AB;Milligan G
通讯作者：
Milligan G
影响因子：
4.8
作者：
Kuszak, Adam J.;Pitchiaya, Sethuramasundaram;Sunahara, Roger K.
通讯作者：
Sunahara, Roger K.
影响因子：
48
作者：
Cranfill PJ;Sell BR;Baird MA;Allen JR;Lavagnino Z;de Gruiter HM;Kremers GJ;Davidson MW;Ustione A;Piston DW
通讯作者：
Piston DW
影响因子：
3.4
作者：
Godin, Antoine G.;Rappaz, Benjamin;Wisemant, Paul W.
通讯作者：
Wisemant, Paul W.
影响因子：
46.9
作者：
Keppler, A;Gendreizig, S;Johnsson, K
通讯作者：
Johnsson, K