Distinct Roles for the Actin Nucleators Arp2/3 and hDia1 during NK-Mediated Cytotoxicity
Distinct Roles for the Actin Nucleators Arp2/3 and hDia1 during NK-Mediated Cytotoxicity
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DOI：
10.1016/j.cub.2009.10.029
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发表时间：
2009-12-01
期刊：
影响因子：
9.2
通讯作者：
Cooper, John A.
中科院分区：
文献类型：
--
作者：
Butler, Boyd;Cooper, John A.
背景资料：几个肌动蛋白成核剂，包括Arp 2/3和各种formin，控制许多细胞内的功能在vivo.Results：我们调查了这些成核剂的相对作用。作为一个模型系统，我们使用自然杀伤（NK）淋巴细胞，它显示了广泛的细胞毒性为基础的功能，最终在靶细胞的裂解。缺乏Arp 2/3或Arp 2Dia 1的NK细胞在靶细胞裂解中无效，但原因不同。Arp 2/3功能的丧失导致与靶细胞连接处的细胞粘附和肌动蛋白组装的缺陷（裂解性突触）。与此相反，hDia 1的损失并没有破坏肌动蛋白组装在裂解突触。相反，损失的hDia 1导致微管细胞骨架中的扰动，包括针对微管的裂解synapse.Conclusions：这些研究揭示了新的区别和Arp 2/3，formin，和微管在细胞中的功能之间的关系。值得注意的是，微管介导细胞周围微管的捕获。
Background: Several actin nucleators, including Arp2/3 and various formins, control numerous cytoskeletal-based functions in vivo.Results: We investigated the relative roles of these nucleators. As a model system, we used natural killer (NK) lymphocytes, which display a wide range of cytoskeletal-based functions that culminate in the lysis of target cells. NK cells lacking either Arp2/3 or the formin hDia1 were ineffective in target cell lysis, but for distinct reasons. Loss of Arp2/3 function led to defects in cell adhesion and actin assembly at the junction with the target cell (the lytic synapse). In contrast, loss of hDia1 did not disrupt actin assembly at the lytic synapse. Instead, loss of hDia1 led to perturbations in the microtubule cytoskeleton, including the targeting of microtubules to the lytic synapse.Conclusions: These studies reveal novel distinctions and relationships among the functions of Arp2/3, formins, and microtubules in cells. Notably, a formin mediates the capture of microtubules at the cell periphery.