Division of Biomedical Sciences and Graduate Program in Cell, Molecular and Developmental Biology, University of California, Riverside, CA, USA.
Mol Pharmacol. 2011 Nov;80(5):760-8. doi: 10.1124/mol.111.072470. Epub 2011 Aug 11.
First identified as mediators of G-protein-coupled receptor desensitization and internalization and later as signaling platforms, β-arrestins play a requisite role in chemotaxis and reorganization of the actin cytoskeleton, downstream of multiple receptors. However, the precise molecular mechanisms underlying their involvement have remained elusive. Initial interest in β-arrestins as facilitators of cell migration and actin reorganization stemmed from the known interplay between receptor endocytosis and actin filament formation, because disruption of the actin cytoskeleton inhibits these β-arrestin-dependent events. With growing interest in the mechanisms by which cells can sense a gradient of agonist during cell migration, investigators began to hypothesize that β-arrestins may contribute to directed migration by controlling chemotactic receptor turnover at the plasma membrane. Finally, increasing evidence emerged that β-arrestins are more than just clathrin adaptor proteins involved in turning off receptor signals; they are actually capable of generating their own signals by scaffolding signaling molecules and controlling the activity of multiple cellular enzymes. This new role of β-arrestins as signaling scaffolds has led to the hypothesis that they can facilitate cell migration by sequestering actin assembly activities and upstream regulators of actin assembly at the leading edge. This Minireview discusses recent advances in our understanding of how β-arrestin scaffolds contribute to cell migration, focusing on recently identified β-arrestin interacting proteins and phosphorylation targets that have known roles in actin reorganization.
β-arrestins 最初被鉴定为 G 蛋白偶联受体脱敏和内化的介质，后来又被鉴定为信号平台，在多种受体的下游，β-arrestins 在趋化作用和肌动蛋白细胞骨架的重排中发挥必需作用。然而，其参与的精确分子机制仍然难以捉摸。β-arrestins 作为细胞迁移和肌动蛋白重排的促进剂的最初兴趣源于受体内吞作用和肌动蛋白丝形成之间的已知相互作用，因为肌动蛋白细胞骨架的破坏会抑制这些依赖β-arrestin 的事件。随着人们对细胞在细胞迁移过程中如何感知激动剂梯度的机制的兴趣日益浓厚，研究人员开始假设β-arrestins 可能通过控制质膜上趋化性受体的周转率来促进定向迁移。最后，越来越多的证据表明，β-arrestins 不仅仅是参与关闭受体信号的网格蛋白衔接蛋白；它们实际上能够通过支架信号分子和控制多种细胞酶的活性来产生自己的信号。β-arrestins 作为信号支架的这种新作用导致了这样一种假设，即它们可以通过在前沿隔离肌动蛋白组装活性和肌动蛋白组装的上游调节剂来促进细胞迁移。这篇综述讨论了我们对β-arrestin 支架如何促进细胞迁移的理解的最新进展，重点介绍了最近鉴定的β-arrestin 相互作用蛋白和磷酸化靶标，这些蛋白和靶标在肌动蛋白重排中具有已知作用。
