Transient Acceleration of Epidermal Growth Factor Receptor Dynamics Produces Higher-Order Signaling Clusters
Transient Acceleration of Epidermal Growth Factor Receptor Dynamics Produces Higher-Order Signaling Clusters
复制标题
DOI：
10.1016/j.jmb.2018.02.018
复制
发表时间：
2018-04-27
影响因子：
5.6
通讯作者：
Sako, Yasushi
中科院分区：
文献类型：
--
作者：
Hiroshima, Michio;Pack, Chan-gi;Sako, Yasushi
细胞信号传导依赖于时空调节的分子相互作用。虽然已经用各种技术分析了信号蛋白的运动，但空间动力学如何影响信号蛋白的分子相互作用尚不清楚。在这里，我们开发了一种单分子方法来分析运动，聚类和信号之间的时空耦合。该分析是用表皮生长因子受体（EGFR）进行的，EGFR在与EGF结合后通过其二聚化和磷酸化触发信号传导。我们的研究结果表明，在膜子域中分离的几个EGFR被释放的EGF依赖增加其扩散面积，促进分子协会和生产不动的集群。使用双色单分子分析，我们发现EGF诱导的状态转变改变了固定簇的性质，使它们能够与细胞质蛋白GRB 2长时间相互作用。我们的研究揭示了这种分子相互作用及其中尺度动力学之间的新的相关性，提供了初始信号节点。(C)2018爱思唯尔有限公司版权所有
Cell signaling depends on spatiotemporally regulated molecular interactions. Although the movements of signaling proteins have been analyzed with various technologies, how spatial dynamics influence the molecular interactions that transduce signals is unclear. Here, we developed a single-molecule method to analyze the spatiotemporal coupling between motility, clustering, and signaling. The analysis was performed with the epidermal growth factor receptor (EGFR), which triggers signaling through its dimerization and phosphorylation after association with EGF. Our results show that the few EGFRs isolated in membrane subdomains were released by an EGF-dependent increase in their diffusion area, facilitating molecular associations and producing immobile clusters. Using a two-color single-molecule analysis, we found that the EGF-induced state transition alters the properties of the immobile clusters, allowing them to interact for extended periods with the cytoplasmic protein, GRB2. Our study reveals a novel correlation between this molecular interaction and its mesoscale dynamics, providing the initial signaling node. (C) 2018 Elsevier Ltd. All rights reserved.