Regulation of mu opioid receptor internalization by the scaffold protein RanBPM.
Regulation of mu opioid receptor internalization by the scaffold protein RanBPM.
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DOI：
10.1016/j.neulet.2009.09.048
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发表时间：
2009-12-11
影响因子：
2.5
通讯作者：
Murrin LC
中科院分区：
文献类型：
--
作者：
Talbot JN;Skifter DA;Bianchi E;Monaghan DT;Toews ML;Murrin LC
Mu阿片受体（MOP）是许多阿片类药物的药理作用（包括镇痛和耐受/依赖）的转换器。以前，我们观察到增加MOP信号在出生后的发展，这是不相关的MOP或G蛋白表达增加。酵母双杂交筛选的人脑cDNA文库使用MOP C-末端作为诱饵确定RanBPM作为一个潜在的MOP相互作用蛋白。RanBPM被认为是一种多功能支架蛋白，可与多种信号受体/蛋白相互作用。HEK 293细胞中的免疫共沉淀研究表明RanBPM与MOP组成性缔合。在功能上，RanBPM对MOP介导的腺苷酸环化酶抑制没有影响，但减少激动剂诱导的MOP内吞作用。从机制上讲，RanBPM干扰MOP刺激的β arrestin 2-GFP易位，但不干扰α 1B-肾上腺素能受体激活，表明作用的选择性。我们的研究结果表明，RanBPM是一种新的MOP相互作用的蛋白质，负调节受体内化，而不改变MOP信号通过腺苷酸环化酶。
Mu opioid receptors (MOP) are transducers of the pharmacological effects of many opioid drugs, including analgesia and tolerance/dependence. Previously, we observed increased MOP signaling during postnatal development that was not associated with increased MOP or G protein expression. A yeast two-hybrid screen of a human brain cDNA library using the MOP C-terminus as bait identified RanBPM as a potential MOP-interacting protein. RanBPM has been recognized as a multi-functional scaffold protein that interacts with a variety of signaling receptors/proteins. Co-immunoprecipitation studies in HEK293 cells indicated that RanBPM constitutively associates with MOP. Functionally, RanBPM had no effect on MOP-mediated inhibition of adenylyl cyclase, yet reduced agonist-induced endocytosis of MOP. Mechanistically, RanBPM interfered with βarrestin2-GFP translocation stimulated by MOP but not α1B-adrenergic receptor activation, indicating selectivity of action. Our findings suggest that RanBPM is a novel MOP-interacting protein that negatively regulates receptor internalization without altering MOP signaling through adenylyl cyclase.
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DOI：
10.1016/s0165-3806(97)00135-1
发表时间：
1997-12-19
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Coulter, CL;Happe, HK;Murrin, LC
通讯作者：
Murrin, LC
有助于增加海洛因成瘾风险或防止海洛因成瘾的基因型模式
影响因子：
11
作者：
Nielsen, D. A.;Ji, F.;Kreek, M. J.
通讯作者：
Kreek, M. J.
影响因子：
4.8
作者：
Feng, GJ;Kellett, E;Milligan, G
通讯作者：
Milligan, G
影响因子：
6.2
作者：
Murrin, L. Charles;Talbot, Jeffery N.
通讯作者：
Talbot, Jeffery N.
DOI：
10.1073/pnas.93.17.9241
发表时间：
1996-08-20
影响因子：
11.1
作者：
Sternini, C;Spann, M;Brecha, NC
通讯作者：
Brecha, NC