Rab5a Regulates Surface Expression of FcεRI and Functional Activation in Mast Cells
Rab5a Regulates Surface Expression of FcεRI and Functional Activation in Mast Cells
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DOI：
10.1248/bpb.34.760
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发表时间：
2011-05-01
影响因子：
2
通讯作者：
Kadowaki, Makoto
中科院分区：
文献类型：
--
作者：
Kageyama-Yahara, Natsuko;Suehiro, Yoko;Kadowaki, Makoto
肥大细胞表面高亲和力免疫球蛋白E受体(Fc Epsilon RI)的表达水平受细胞膜的结构性内化调控，这被认为是Fc epsilon RI介导的信号潜能的重要决定因素。然而，Fc epsilon RI转运的分子机制仍然知之甚少。RAB蛋白是一种小的鸟苷5‘-三磷酸酶(GTP酶)，参与膜运输的调节。特别是，Rab5已被证明在早期内吞途径中调节转运，但尚不清楚Fc epsilon RI表面表达水平是否受Rab5的调节。在本研究中，我们通过小干扰RNA敲除方法研究了单个Rab5亚型在肥大细胞中的作用。我们的结果表明，Rab5a基因敲除增强了Fc epsilon RI依赖的肥大细胞的激活，并在其稳定状态下上调了Fc epsilon RI表面的表达。相反，Rab5c基因敲除导致激活被抑制。这些发现揭示了Rab5亚型在肥大细胞功能中的调节作用和个体作用。
Surface expression levels of high-affinity immunoglobulin E (IgE) receptors (Fc epsilon RI) on mast cells are regulated by constitutive internalization from the plasma membrane, which is thought to be an important determinant of Fc epsilon RI-mediated signaling potential. However, molecular mechanism of Fc epsilon RI trafficking has remained poorly understood. Rab proteins are small guanosine 5'-triphosphatases (GTPases) involved in the regulation of membrane traffic. In particular, Rab5 has been shown to regulate transport in the early endocytic pathway, whereas it is not known whether the Fc epsilon RI surface expression levels are regulated by Rab5. In this study, we investigated the role of individual Rab5 isoforms in mast cells by small interfering RNA knockdown method. Our results demonstrate that Rab5a knockdown enhanced Fc epsilon RI-dependent mast cell activation and upregulated Fc epsilon RI surface expression in its steady state. In contrast, Rab5c knockdown caused suppression of the activation. These findings revealed modulatory and individual roles of Rab5 isoforms in mast cell functions.