β-arrestin mediates communication between plasma membrane and intracellular GPCRs to regulate signaling.
β-arrestin mediates communication between plasma membrane and intracellular GPCRs to regulate signaling.
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DOI：
10.1038/s42003-020-01510-2
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发表时间：
2020-12-18
影响因子：
5.9
通讯作者：
Liu AP
中科院分区：
文献类型：
--
作者：
DeNies MS;Smrcka AV;Schnell S;Liu AP
越来越明显的是，G蛋白偶联受体（GPCR）定位是细胞信号传导的主要调节因子。然而，在这个过程中涉及的分子机制还没有很好地理解。到目前为止，观察细胞内GPCR激活可以分为两类：依赖于OCT 3阳离子通道渗透配体或内吞运输的必要性。使用CXC趋化因子受体4（CXCR 4）作为模型，我们鉴定了细胞内GPCR信号传导的第三种机制。我们表明，独立的膜渗透配体和内吞作用，刺激后，质膜和内部池的CXCR 4的后修饰和共同调节EGR 1转录。我们发现β-arrestin-1（arrestin 2）是介导质膜和CXCR 4内部池之间通讯所必需的。值得注意的是，这些观察结果可以解释，虽然CXCR 4过表达与癌症转移和死亡率高度相关，但质膜定位与此无关。这些数据共同支持了一个模型，其中质膜定位的GPCR的小的初始池能够激活内部受体依赖性信号传导事件。DeNies等人确定了细胞内GPCR信号传导的新机制。使用CXC趋化因子受体4（CXCR 4）作为模型，他们表明，在用受体激动剂刺激后，不仅质膜定位的受体，而且细胞内CXCR 4分子都被后修饰并调节转录。这项研究表明，一小部分质膜定位的GPCR可以激活内部受体依赖性信号，β-arrestin-1介导了这种激活。
It has become increasingly apparent that G protein-coupled receptor (GPCR) localization is a master regulator of cell signaling. However, the molecular mechanisms involved in this process are not well understood. To date, observations of intracellular GPCR activation can be organized into two categories: a dependence on OCT3 cationic channel-permeable ligands or the necessity of endocytic trafficking. Using CXC chemokine receptor 4 (CXCR4) as a model, we identified a third mechanism of intracellular GPCR signaling. We show that independent of membrane permeable ligands and endocytosis, upon stimulation, plasma membrane and internal pools of CXCR4 are post-translationally modified and collectively regulate EGR1 transcription. We found that β-arrestin-1 (arrestin 2) is necessary to mediate communication between plasma membrane and internal pools of CXCR4. Notably, these observations may explain that while CXCR4 overexpression is highly correlated with cancer metastasis and mortality, plasma membrane localization is not. Together these data support a model where a small initial pool of plasma membrane-localized GPCRs are capable of activating internal receptor-dependent signaling events. DeNies et al. identify a new mechanism of intracellular GPCR signalling. Using CXC chemokine receptor 4 (CXCR4) as a model, they show that upon stimulation with receptor agonists that not only plasma membrane-localized receptors, but also intracellular CXCR4 molecules are post-translationally modified and regulate transcription. This study suggests that a small pool of plasma membrane-localized GPCRs can activate internal receptor-dependent signaling, and that β-arrestin-1 mediates this activation.
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影响因子：
64.8
作者：
Eichel K;Jullié D;Barsi-Rhyne B;Latorraca NR;Masureel M;Sibarita JB;Dror RO;von Zastrow M
通讯作者：
von Zastrow M
影响因子：
4.8
作者：
Azpiazu, Inaki;Akgoz, Muslum;Gautam, N.
通讯作者：
Gautam, N.
影响因子：
4.8
作者：
Irannejad, Roshanak;Wedegaertner, Philip B.
通讯作者：
Wedegaertner, Philip B.
DOI：
10.1073/pnas.95.16.9448
发表时间：
1998-08-04
影响因子：
11.1
作者：
Ma, Q;Jones, D;Springer, TA
通讯作者：
Springer, TA
影响因子：
8
作者：
Luker, K. E.;Lewin, S. A.;Mihalko, L. A.;Schmidt, B. T.;Winkler, J. S.;Coggins, N. L.;Thomas, D. G.;Luker, G. D.
通讯作者：
Luker, G. D.