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首页> 外文期刊>Current Biology: CB >The WAVE2 complex regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation
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The WAVE2 complex regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation

机译：WAVE2复合物在T细胞活化过程中调节肌动蛋白细胞骨架重组和CRAC介导的钙进入

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BACKGROUND: The engagement of the T cell receptor results in actin cytoskeletal reorganization at the immune synapse (IS) and the triggering of biochemical signaling cascades leading to gene regulation and, ultimately, cellular activation. Recent studies have identified the WAVE family of proteins as critical mediators of Rac1-induced actin reorganization in other cell types. However, whether these proteins participate in actin reorganization at the IS or signaling pathways in T cells has not been investigated. RESULTS: By using a combination of biochemical, genetic, and cell biology approaches, we provide evidence that WAVE2 is recruited to the IS, is biochemically modified, and is required for actin reorganization and beta-integrin-mediated adhesion after TCR crosslinking. Moreover, we show that WAVE2 regulates calcium entry at a point distal to PLCgamma1 activation and IP(3)-mediated store release. CONCLUSIONS: These data reveal a role for WAVE2 in regulating multiple pathways leading to T cell activation. In particular, this work shows that WAVE2 is a key component of the actin regulatory machinery in T cells and that it also participates in linking intracellular calcium store depletion to calcium release-activated calcium (CRAC) channel activation.
机译：背景：T细胞受体的参与导致免疫突触（IS）的肌动蛋白细胞骨架重组，并触发生化信号传导级联，从而导致基因调节，最终导致细胞活化。最近的研究已经将WAVE蛋白家族确定为其他细胞类型中Rac1诱导的肌动蛋白重组的关键介体。然而，尚未研究这些蛋白是否参与IS的肌动蛋白重组或T细胞中的信号通路。结果：通过结合使用生物化学，遗传和细胞生物学方法，我们提供证据表明WAVE2被招募到IS，经过生物化学修饰，是TCR交联后肌动蛋白重组和β-整合素介导的粘附所必需的。此外，我们表明WAVE2调节钙离子进入PLCgamma1激活和IP（3）介导的存储释放的远端。结论：这些数据揭示了WAVE2在调节导致T细胞活化的多种途径中的作用。特别地，这项工作表明WAVE2是T细胞中肌动蛋白调节机制的关键组成部分，并且它还参与将细胞内钙存储耗竭与钙释放激活钙（CRAC）通道激活联系起来。

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