The signaling adaptor Eps8 is an essential actin capping protein for dendritic cell migration.

The signaling adaptor Eps8 is an essential actin capping protein for dendritic cell migration.
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DOI:
10.1016/j.immuni.2011.07.007
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发表时间:
2011-09-23
期刊:
影响因子:
32.4
通讯作者:
Scita G
Scita G
中科院分区:
医学1区
文献类型:
--
作者:
Frittoli E;Matteoli G;Palamidessi A;Mazzini E;Maddaluno L;Disanza A;Yang C;Svitkina T;Rescigno M;Scita G

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树突状细胞(DC)通过使用不同的迁移策略来灵活地适应不同的微环境,这些策略最终依赖于肌动蛋白细胞骨架的动态和结构组织。在这里,我们已经表明,DC需要信号适配器EPS8的肌动蛋白封顶活性来极化并形成细长的迁移突起。Eps8基因缺陷小鼠的树突状细胞在体外3d定向和趋化迁移受损,炎症攻击后延迟到达体内引流淋巴结(DLN)。因此,EPS8基因缺陷的小鼠不能产生接触性超敏反应。我们还证明了DC迁移缺陷是细胞自主的,并且Eps8是肌动蛋白网络的适当结构组织和细胞突起的动力学所必需的。然而,Eps8不是抗原摄取、处理和呈递所必需的。因此,我们已经确定Eps8是一种独特的肌动蛋白封帽蛋白,特别是DC迁移所需的。
Dendritic cells (DCs) flexibly adapt to different microenvironments by using diverse migration strategies that are ultimately dependent on the dynamics and structural organization of the actin cytoskeleton. Here, we have shown that DCs require the actin capping activity of the signaling adaptor Eps8 to polarize and to form elongated migratory protrusions. DCs from Eps8-deficient mice are impaired in directional and chemotactic migration in 3D in vitro and are delayed in reaching the draining lymph node (DLN) in vivo after inflammatory challenge. Hence, Eps8-deficient mice are unable to mount a contact hypersensitivity response. We have also shown that the DC migratory defect is cell autonomous and that Eps8 is required for the proper architectural organization of the actin meshwork and dynamics of cell protrusions. Yet, Eps8 is not necessary for antigen uptake, processing, and presentation. Thus, we have identified Eps8 as a unique actin capping protein specifically required for DC migration.
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