Department of Chemistry, Indiana University, Bloomington, IN 47405-7102, USA.
J Cell Sci. 2013 Mar 1;126(Pt 5):1049-58. doi: 10.1242/jcs.098210.
The actin cytoskeleton provides a dynamic framework to support membrane organization and cellular signaling events. The importance of actin in T cell function has long been recognized to go well beyond the maintenance of cell morphology and transport of proteins. Over the past several years, our understanding of actin in T cell activation has expanded tremendously, in part owing to the development of methods and techniques to probe the complex interplay between actin and T cell signaling. On the one hand, biochemical methods have led to the identification of many key cytoskeleton regulators and new signaling pathways, whereas, on the other, the combination of advanced imaging techniques and physical characterization tools has allowed the spatiotemporal investigation of actin in T cell signaling. All those studies have made a profound impact on our understanding of the actin cytoskeleton in T cell activation. Many previous reviews have focused on the biochemical aspects of the actin cytoskeleton. However, here we will summarize recent studies from a biophysical perspective to explain the mechanistic role of actin in modulating T cell activation. We will discuss how actin modulates T cell activation on multiple time and length scales. Specifically, we will reveal the distinct roles of the actin filaments in facilitating TCR triggering, orchestrating 'signalosome' assembly and transport, and establishing protein spatial organization in the immunological synapse.
肌动蛋白细胞骨架为膜组织和细胞信号事件提供了一个动态的支撑框架。肌动蛋白在 T 细胞功能中的重要性早已被广泛认可，它远远超出了维持细胞形态和蛋白质运输的功能。在过去的几年中，我们对 T 细胞激活中肌动蛋白的理解有了极大的扩展，这在一定程度上要归功于开发了探测肌动蛋白与 T 细胞信号之间复杂相互作用的方法和技术。一方面，生化方法导致了许多关键细胞骨架调节剂和新的信号通路的鉴定，另一方面，高级成像技术和物理特性分析工具的结合使得对 T 细胞信号中肌动蛋白的时空研究成为可能。所有这些研究都对我们理解 T 细胞激活中的肌动蛋白细胞骨架产生了深远的影响。许多以前的综述都集中在肌动蛋白细胞骨架的生化方面。然而，在这里，我们将从生物物理的角度总结最近的研究，以解释肌动蛋白在调节 T 细胞激活中的机械作用。我们将讨论肌动蛋白如何在多个时间和长度尺度上调节 T 细胞的激活。具体来说，我们将揭示肌动蛋白丝在促进 TCR 触发、协调“信号小体”组装和运输以及在免疫突触中建立蛋白质空间组织方面的独特作用。
