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中文摘要：
阿片受体的信号传导受到多种细胞内外因素的严格调控.β-arrestin作为一类重要的细胞浆信号负调节蛋白和支架蛋白在阿片类药物诱导的阿片受体内吞中起关键作用.我们的研究发现阿片受体存在受体磷酸化依赖和不依赖的两种受体内吞机制.β-arrestin2为受体磷酸化依赖的内吞所必需,而β-arrestin1主要参与磷酸化非依赖的阿片受体内吞过程.近期的研究发现,β-arrestin作为一类重要的脚手架蛋白,不仅可以通过其不同的亚型对阿片受体的内吞进行精确调控,还可以与特定的基因启动子结合,通过招募乙酰化酶增加局部组蛋白乙酰化水平、上调基因转录,从而通过表观遗传学修饰机制将阿片受体信号从细胞膜直接传递至细胞核.本文主要介绍这一方面研究的初步进展.
英文摘要：
Opioid receptor- mediated signal transduction is regulated by many extracellular and intracellular factors. β - arrestins, key negative regulators and scaffolds of G protein - coupled receptor signaling, play an important role in regulation of opioid receptor - mediated signal transduction. Our results indicated the presence of an agonist - induced, receptor phosphorylaton - independent mechanism for internalization of delta - opioid receptors （DORs）. Further study showed that β - arrestin2 is required for the phosphorylation - independent DOR internalization, whereas β - arrestinl functions mainly in the phosphorylation- dependent DOR internalization. Our study showed that β - arrestinl also function as a nuclear messenger of DOR. β - arrestinl regulates histone modification and gene transcription, which is an epigenetic mechanism for opioid receptor- mediated extracellular transmitted through the cytoplasm to the nucleus. signals
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