Type-1 cannabinoid receptors colocalize with caveolin-1 in neuronal cells.

Type-1 cannabinoid receptors colocalize with caveolin-1 in neuronal cells.
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DOI:
10.1016/j.neuropharm.2007.06.030
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发表时间:
2008-01
期刊:
影响因子:
4.7
通讯作者:
Maccarrone M
Maccarrone M
中科院分区:
医学2区
文献类型:
--
作者:
Bari M;Oddi S;De Simone C;Spagnolo P;Gasperi V;Battista N;Centonze D;Maccarrone M

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类型-1(CB1)和类型-2(CB2)大麻素受体属于视紫红质G蛋白偶联受体家族,由内源性脂质激活,称为内源性大麻素。最近的报道表明,与CB2R和其他内源性大麻素的受体和代谢酶不同,CB1R在脂筏中发挥作用,即质膜微区,可能在调节信号转导中起重要作用。在这里,我们提供了基于细胞亚分离、免疫沉淀和共聚焦显微镜研究的新数据,这些数据表明在C6细胞中,CB1R几乎完全与小窝蛋白-1共定位。我们还表明,CB1R对RAFT干扰物甲基-β-环糊精(MCD)的转运是与小窝蛋白-1重叠的,并且MCD处理增加了CB1R与其特异性抗体的可及性。这些发现可能与内源性大麻素依赖CB1R的多种活动有关,如对细胞凋亡和神经退行性疾病的调节。
Type-1 (CB1) and type-2 (CB2) cannabinoid receptors belong to the rhodopsin family of G protein-coupled receptors, and are activated by endogenous lipids termed “endocannabinoids”. Recent reports have demonstrated that CB1R, unlike CB2R and other receptors and metabolic enzymes of endocannabinoids, functions in the context of lipid rafts, i.e. plasma membrane microdomains which may be important in modulating signal transduction. Here, we present novel data based on cell subfractionation, immunoprecipitation and confocal microscopy studies, that show that in C6 cells CB1R co-localizes almost entirely with caveolin-1. We also show that trafficking of CB1R in response to the raft disruptor methyl-β-cyclodextrin (MCD) is superimposable on that of caveolin-1, and that MCD treatment increases the accessibility of CB1R to its specific antibodies. These findings may be relevant for the manifold CB1R-dependent activities of endocannabinoids, like the regulation of apoptosis and of neurodegenerative diseases.
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