Small, Mobile FcεR1 Receptor Aggregates Are Signaling Competent
Small, Mobile FcεR1 Receptor Aggregates Are Signaling Competent
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DOI：
10.1016/j.immuni.2009.06.026
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发表时间：
2009-09-18
期刊：
影响因子：
32.4
通讯作者：
Lidke, Diane S.
中科院分区：
文献类型：
--
作者：
Andrews, Nicholas L.;Pfeiffer, Janet R.;Lidke, Diane S.
ige结合的Fc epsilon R1交联触发肥大细胞脱颗粒。先前的光漂白后荧光恢复（FRAP）和磷光各向异性研究表明，Fc epsilon R1必须固定才能发出信号。在这里，单量子点（QD）跟踪和高光谱显微镜方法被用来定义受体迁移和信号之间的关系。至少三个受体的QD-IgE-Fc epsilon R1聚集体在诱导Syk激酶激活和接近最大分泌的低浓度抗原下保持高度移动过长时间。以DNP-QD形式呈现的多价抗原在低剂量下也保持流动性，支持分泌。在中等和高抗原浓度下，Fc epsilon R1的固定化被标记，与簇大小和受体内化率的增加相关。激酶抑制剂PP2阻断分泌，但不影响固定化或内化。我们认为，不动性是高度交联免疫受体聚集的一个特征，也是受体内化的一个触发因素，但不是酪氨酸激酶激活导致分泌所必需的。
Crosslinking of IgE-bound Fc epsilon R1 triggers mast cell degranulation. Previous fluorescence recovery after photobleaching (FRAP) and phosphorescent anisotropy studies suggested that Fc epsilon R1 must immobilize to signal. Here, single quantum dot (QD) tracking and hyperspectral microscopy methods were used for defining the relationship between receptor mobility and signaling. QD-IgE-Fc epsilon R1 aggregates of at least three receptors remained highly mobile overextended times at low concentrations of antigen that induced Syk kinase activation and near-maximal secretion. Multivalent antigen, presented as DNP-QD, also remained mobile at low doses that supported secretion. Fc epsilon R1 immobilization was marked at intermediate and high antigen concentrations, correlating with increases in cluster size and rates of receptor internalization. The kinase inhibitor PP2 blocked secretion without affecting immobilization or internalization. We propose that immobility is a feature of highly crosslinked immunoreceptor aggregates and a trigger for receptor internalization, but is not required for tyrosine kinase activation leading to secretion.