Actin cytoskeleton reorganization by Syk regulates Fcγ receptor responsiveness by increasing its lateral mobility and clustering.
Actin cytoskeleton reorganization by Syk regulates Fcγ receptor responsiveness by increasing its lateral mobility and clustering.
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DOI：
10.1016/j.devcel.2014.04.031
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发表时间：
2014-06-09
影响因子：
11.8
通讯作者：
Grinstein, Sergio
中科院分区：
文献类型：
--
作者：
Jaumouille, Valentin;Farkash, Yoav;Jaqaman, Khuloud;Das, Raibatak;Lowell, Clifford A.;Grinstein, Sergio
免疫受体在与多价配体缔合后的聚集触发重要的应答，包括吞噬作用、细胞因子分泌和免疫球蛋白产生。我们应用单分子检测和跟踪方法研究了控制吞噬细胞Fcγ受体（FcγR）迁移和聚集的因素。虽然在静息巨噬细胞中，受体作为单体存在，但基于其移动性，可以辨别出两种不同的群体：一些通过明显的自由运动扩散，而另一些则被限制在亚微米边界内，从而降低自发碰撞的频率。Src家族和Syk激酶决定了肌动蛋白细胞骨架的结构，其是有孔的，解释了FcγR的不均匀扩散。在吞噬作用期间刺激这些激酶可诱导局部和远端细胞骨架重组，从而改变受体迁移率和聚集，产生反馈环，促进FcγR在伪足尖端的结合，指导吞噬作用的进展。
Clustering of immunoreceptors upon association with multivalent ligands triggers important responses including phagocytosis, secretion of cytokines and production of immunoglobulins. We applied single-molecule detection and tracking methods to study the factors that control the mobility and clustering of phagocytic Fcγ receptors (FcγR). While in resting macrophages the receptors exist as monomers, two distinct populations were discernible based on their mobility: some diffuse by apparent free motion, while others are confined within sub-micron boundaries that reduce the frequency of spontaneous collisions. Src-family and Syk kinases determine the structure of the actin cytoskeleton, which is fenestrated, accounting for the heterogeneous diffusion of the FcγR. Stimulation of these kinases during phagocytosis induces reorganisation of the cytoskeleton both locally and distally in a manner that alters receptor mobility and clustering, generating a feedback loop that facilitates engagement of FcγR at the tip of pseudopods, directing the progression of phagocytosis.
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影响因子：
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