Natural killer (NK) cells eliminate abnormal cells through the release of cytolytic granule contents. In this process, NK cells must adhere to target cells through integrin-mediated adhesion, which is highly dependent on the generation of F-actin. Ena/VASP-like (EVL) is an actin regulatory protein previously shown to regulate integrin-mediated adhesion in other cell types, but its role in NK cell biology is not known. Herein, we show that EVL is recruited to the NK cell cytotoxic synapse and is required for NK cell cytotoxicity. Significantly, EVL is involved in the generation of F-actin at the cytotoxic synapse, antibody-stimulated spreading, and NK cell-target cell adhesion. EVL interacts with WASP (also known as WAS) and VASP and is required for localization of both proteins to the synapse. Recruitment of EVL to points of cellular activation occurs through the receptor NKG2D-DAP10 (also known as KLRK1 and HCST, respectively) via a binding site previously implicated in VAV1 and Grb2 recruitment. Taken together, this study implicates DAP10-mediated Grb2 and VAV1 signaling in the recruitment of an EVL-containing actin regulatory complex to the cytotoxic synapse where it can promote F-actin nucleation leading to NK cell-mediated killing.

中文翻译：

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NKG2D-DAP10信号传导将EVL募集到细胞毒性突触中，以产生F-肌动蛋白并促进NK细胞的细胞毒性。

天然杀伤（NK）细胞通过释放溶细胞性颗粒成分来消除异常细胞。在此过程中，NK细胞必须通过整合素介导的粘附作用粘附于靶细胞，而粘附作用高度依赖于F-肌动蛋白的产生。Ena / VASP-like（EVL）是一种肌动蛋白调节蛋白，先前显示其在其他细胞类型中调节整合素介导的粘附，但在NK细胞生物学中的作用尚不清楚。在这里，我们表明，EVL被募集到NK细胞的细胞毒性突触，是NK细胞的细胞毒性所必需的。值得注意的是，EVL参与了细胞毒性突触中F-肌动蛋白的生成，抗体刺激的扩散以及NK细胞与靶细胞的粘附。EVL与WASP（也称为WAS）和VASP相互作用，这是将两种蛋白质定位到突触所必需的。通过受体NKG2D-DAP10（分别也称为KLRK1和HCST），通过先前与VAV1和Grb2募集有关的结合位点，将EVL募集到细胞激活点。两者合计，这项研究牵涉到DAP10介导的Grb2和VAV1信号转导包含EVL的肌动蛋白调节复合物募集到细胞毒性突触，在那里它可以促进F-肌动蛋白成核，从而导致NK细胞介导的杀伤。