Signaling through integrin LFA-1 leads to filamentous actin polymerization and remodeling, resulting in enhanced T cell adhesion
Signaling through integrin LFA-1 leads to filamentous actin polymerization and remodeling, resulting in enhanced T cell adhesion
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DOI：
10.4049/jimmunol.168.12.6330
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发表时间：
2002-06-15
影响因子：
4.4
通讯作者：
Hogg, N
中科院分区：
文献类型：
--
作者：
Porter, JC;Bracke, M;Hogg, N
整合素可以激活信号通路，但这些通路的最终下游结果往往不清楚。本研究分析了白细胞整合素LFA-1与其配体二聚体ICAM-1相互作用引发的信号事件的后果。我们表明，LFA-1的活性形式调节其自身的功能，通过指导F-肌动蛋白细胞骨架的重塑，以加强T细胞粘附ICAM-1的原代人T细胞。共聚焦显微镜显示，在粘附ICAM-1的T细胞中，F-肌动蛋白成束和F-肌动蛋白的总体水平都增加。使用激光扫描细胞仪技术对大量T细胞的F-肌动蛋白水平的增加和F-肌动蛋白分布的变化进行定量，发现其具有显著性。该研究继续表明，构象改变的LFA-1的聚集对于F-肌动蛋白的变化至关重要，并提出了一个模型，其中聚集的高亲和力T细胞LFA-1与多价ICAM-1相互作用，导致LFA-1信号传导，这导致F-肌动蛋白聚合和高阶F-肌动蛋白捆绑。研究结果表明，LFA-1不仅作为粘附受体，而且作为信号受体，通过主动启动F-肌动蛋白重组，这是许多T细胞依赖性过程所必需的。
The integrins can activate signaling pathways, but the final downstream outcome of these pathways is often unclear. This study analyzes the consequences of signaling events initiated by the interaction of the leukocyte integrin LFA-1 with its ligand, dimeric ICAM-1. We show that the active form of LFA-1 regulates its own function on primary human T cells by directing the remodeling of the F-actin cytoskeleton to strengthen T cell adhesion to ICAM-1. Confocal microscopy revealed that both F-actin bundling and overall levels of F-actin are increased in the ICAM-1-adhering T cells. This increase in F-actin levels and change in F-actin distribution was quantitated for large numbers of T cells using the technique of laser scanning cytometry and was found to be significant. The study went on to show that clustering of conformationally altered LFA-1 is essential for the changes in F-actin, and a model is proposed in which clustered, high-avidity T cell LFA-1, interacting with multivalent ICAM-1, causes LFA-1 signaling, which results in F-actin polymerization and higher-order F-actin bundling. The findings demonstrate that LFA-1 acts not only as an adhesion receptor but also as a signaling receptor by actively initiating the F-actin reorganization that is essential for many T cell-dependent processes.