In this study, using Jurkat cells, we show that DISC1 (disrupted in schizophrenia 1) and Girdin (girders of actin filament) are essential for typical actin accumulation at the immunological synapse. Furthermore, DISC1, Girdin and dynein are bound in a complex. Although this complex initially forms as a central patch at the synapse, it relocates to a peripheral ring corresponding to the peripheral supramolecular activation cluster (pSMAC). In the absence of DISC1, the classic actin ring does not form, cell spreading is blocked, and the dynein complex fails to relocate to the pSMAC. A similar effect is seen when Girdin is deleted. When cells are treated with inhibitors of actin polymerization, the dynein–NDE1 complex is lost from the synapse and the microtubule-organizing center fails to translocate, suggesting that actin and dynein might be linked. Upon stimulation of T cell receptors, DISC1 becomes associated with talin, which likely explains why the dynein complex colocalizes with the pSMAC. These results show that the DISC1–Girdin complex regulates actin accumulation, cell spreading and distribution of the dynein complex at the synapse.

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在这项研究中，我们使用 Jurkat 细胞证明 DISC1（在精神分裂症 1 中被破坏）和 Girdin（肌动蛋白丝梁）对于免疫突触处典型肌动蛋白的积累至关重要。此外，DISC1、Girdin 和动力蛋白结合成复合物。尽管该复合体最初形成为突触的中央斑块，但它重新定位到与外周超分子激活簇（pSMAC）相对应的外周环。在缺乏 DISC1 的情况下，经典的肌动蛋白环不会形成，细胞扩散受阻，动力蛋白复合物无法重新定位到 pSMAC。当 Girdin 被删除时，也会出现类似的效果。当细胞用肌动蛋白聚合抑制剂处理时，动力蛋白-NDE1复合物从突触中丢失，微管组织中心无法易位，这表明肌动蛋白和动力蛋白可能是相连的。在刺激 T 细胞受体后，DISC1 与踝蛋白结合，这可能解释了为什么动力蛋白复合物与 pSMAC 共定位。这些结果表明 DISC1-Girdin 复合物调节肌动蛋白积累、细胞扩散和动力蛋白复合物在突触的分布。

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