Department of Medical Biotechnologies and Translational Medicine, University of Milan, I-20089 Rozzano, Italy.
Biochem Soc Trans. 2013 Feb 1;41(1):231-6. doi: 10.1042/BST20120246.
ACRs (atypical chemokine receptors) were initially referred to as 'silent' receptors on the basis of a lack of signalling and functional activities that are typically observed with conventional chemokine receptors. Although ACRs do not directly induce cell migration, they indirectly control leucocyte recruitment by shaping chemokine gradients in tissues through degradation, transcytosis or local concentration of their cognate ligands. Recent evidence also suggests that these biological activities are supported by G-protein-independent, β-arrestin-dependent signalling events. In the present article, we review current knowledge on structural and signalling properties of ACRs that are changing our view on this entire class of receptors from silent to endogenous β-arrestin-biased signalling receptors.
ACRs(非典型趋化因子受体)最初被称为“沉默”受体,这是基于缺乏通常在传统趋化因子受体中观察到的信号转导和功能活性。尽管 ACR 本身不会直接诱导细胞迁移,但它们通过降解、转胞吞作用或局部浓缩其配体,间接控制组织中趋化因子梯度,从而间接控制白细胞募集。最近的证据还表明,这些生物学活性是由 G 蛋白非依赖性、β-arrestin 依赖性信号事件支持的。在本文中,我们综述了 ACR 的结构和信号转导特性的最新知识,这些知识正在改变我们对整个受体类别的看法,即从沉默的到内源性β-arrestin 偏向性信号转导受体。