Dimerization of the delta opioid receptor: Implication for a role in receptor internalization
Dimerization of the delta opioid receptor: Implication for a role in receptor internalization
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DOI：
10.1074/jbc.272.43.26959
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发表时间：
1997-10-24
影响因子：
4.8
通讯作者：
Devi, LA
中科院分区：
文献类型：
--
作者：
Cvejic, S;Devi, LA
G蛋白偶联受体的二聚化在其生物活性的调节中日益受到关注，但其在激动剂诱导的受体内化中的作用还不是很清楚。在这项研究中，我们研究了小鼠阿片受体二聚化的能力，以及受体二聚化在激动剂诱导内化中的作用。使用不同的(Flag和c-Myc)表位标记受体，我们发现增量阿片受体以二聚体的形式存在，二聚化水平是激动剂依赖的，激动剂浓度的增加降低了二聚体的水平，而单体的水平相应增加，有趣的是，吗啡不影响这两种形式的水平，已经表明吗啡不同于其他阿片激动剂，不诱导受体内化。这表明激动剂降低二聚体水平和诱导受体内化的能力之间存在关系，激动剂诱导的增量阿片受体二聚体减少的时间进程短于内化的时间进程，这表明单体作用先于激动剂诱导的受体内化，此外，我们发现C端缺失15个残基的突变的增量阿片受体不会发生二聚化。这种突变的受体已被证明缺乏经历激动剂诱导内化的能力。这些结果表明，二聚体和单体之间的相互转化在阿片受体内化中起作用。
Dimerization of G protein-coupled receptors has been increasingly noted in the regulation of their biological activity, However, its involvement in agonist-induced receptor internalization is not well understood. In this study, we examined the ability of mouse delta-opioid receptors to dimerize and the role of receptor dimerization in agonist induced internalization. Using differentially (Flag and c-Myc) epitope-tagged receptors we show that delta-opioid receptors exist as dimers, The level of dimerization is agonist dependent, Increasing concentrations of agonists reduce the levels of dimer with a corresponding increase in the levels of monomer, Interestingly, morphine does not affect the levels of either form, It has been shown that morphine, unlike other opioid agonists, does not induce receptor internalization. This suggests a relationship between the ability of agonists to reduce the levels of dimer and to induce receptor internalization, The time course of the agonist-induced decrease of delta-opioid receptor dimers is shorter than the time course of internalization, suggesting that monomerization precedes the agonist-induced internalization of the receptor, Furthermore, we found that a mutant delta-opioid receptor, with a 15-residue C-terminal deletion, does not exhibit dimerization. This mutant receptor has been shown to lack the ability to undergo agonist-induced internalization. These results suggest that the interconversion between the dimeric and monomeric forms plays a role in opioid receptor internalization.