Formation of signal transduction complexes during immobile phase of NGFR movements
Formation of signal transduction complexes during immobile phase of NGFR movements
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DOI：
10.1016/j.bbrc.2006.01.126
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发表时间：
2006-03-31
影响因子：
3.1
通讯作者：
Sako, Y
中科院分区：
文献类型：
--
作者：
Shibata, SC;Hibino, K;Sako, Y
神经生长因子(NGF)是一种分泌型神经营养因子，参与神经元的分化、生长和维持。在这里，我们使用单分子成像来表征Cy3标记的NGF与PC12细胞表面的受体复合体结合后的行为。我们发现，NGF受体复合体有两种不同的扩散状态，分别为流动相和固定相。两种扩散态之间的转变是可逆的，持续时间由单一限速过程决定。向固定相的突然转变往往与NGF受体复合体的聚集同时发生。固定化依赖于TrkA NGF受体的磷酸化。利用双色成像技术证实，细胞间信号蛋白的膜募集与NGF受体复合体一起发生在固定期，表明信号转导发生在这一阶段。因此，NGF信号通过一个重复的随机过程来诱导信号复合体的瞬时形成。(C)2006 Elsevier Inc.保留所有权利。
Nerve growth factor (NGF) is a secreted neurotrophin involved in the differentiation, growth, and maintenance of neurons. Here, we have used single-molecule imaging to characterize the behavior of Cy3-tagged NGF after binding to receptor complexes on the surfaces of PC12 cells. We show that NGF-receptor complexes have two distinct diffusive states, characterized as mobile and immobile phase. The transition between the two diffusive states occurred reversibly with duration times determined by a single rate limiting process. The abrupt transition to the immobile phase often occurred simultaneously with the clustering of NGF-receptor complexes. Immobilization depended on the phosphorylation of the TrkA NGF-receptor. Using dual-color imaging, it was demonstrated that the membrane recruitment of the intercellular signaling protein occurs with NGF-receptor complexes in the immobile phase indicating signal transduction occurs during this phase. Thus, NGF signaling is performed through a repetitive random process to induce transient formation of signaling complexes. (c) 2006 Elsevier Inc. All rights reserved.