Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030.
Proc Natl Acad Sci U S A. 2014 May 6;111(18):6708-13. doi: 10.1073/pnas.1314975111. Epub 2014 Apr 23.
Lytic immune effector function depends upon directed secretion of cytolytic granules at the immunological synapse (IS) and requires dynamic rearrangement of filamentous (F)-actin. Coronin 1A (Coro1A) is the hematopoietic-specific member of the Coronin family of actin regulators that promote F-actin disassembly. Here, we show that Coro1A is required for natural killer (NK) cell cytotoxic function in two human NK cell lines and ex vivo cells from a Coro1A-deficient patient. Using superresolution nanoscopy to probe the IS, we demonstrate that Coro1A promotes the deconstruction of F-actin density that facilitates effective delivery of lytic granules to the IS. Thus, we show, for the first time to our knowledge, a critical role for F-actin deconstruction in cytotoxic function and immunological secretion and identify Coro1A as its mediator.
溶细胞免疫效应功能依赖于免疫突触（IS）中溶细胞颗粒的定向分泌，这需要丝状（F）-肌动蛋白的动态重排。冠蛋白 1A（Coro1A）是肌动蛋白调节因子冠蛋白家族中的造血特异性成员，可促进 F-肌动蛋白解体。在这里，我们表明 Coro1A 是人自然杀伤（NK）细胞两种 NK 细胞系和 Coro1A 缺陷患者的体外细胞中细胞毒性功能所必需的。我们使用超分辨率纳米显微镜探测 IS，证明 Coro1A 促进 F-肌动蛋白密度的解构，从而有利于有效地将溶细胞颗粒递送到 IS。因此，我们首次表明，F-肌动蛋白的解构在细胞毒性功能和免疫分泌中起着关键作用，并确定 Coro1A 是其介质。
