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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A specific role of AGS3 in the surface expression of plasma membrane proteins
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A specific role of AGS3 in the surface expression of plasma membrane proteins

机译：AGS3在质膜蛋白表面表达中的特定作用

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摘要

Activator of G protein signaling 3 (AGS3), originally identified in a functional screen for mammalian proteins that activate heterotrimeric G protein signaling, is known to be involved in drug-seeking behavior and is up-regulated during cocaine withdrawal in animal models. These observations indicate a potential role for AGS3 in the formation or maintenance of neural plasticity. We have found that the overexpression of AGS3 alters the surface-to-total ratios of a subset of heterologously expressed plasma membrane receptors and channels. Further analysis of the endocytic trafficking of one such protein by a biotin-based internalization assay suggests that overexpression of AGS3 moderately affects the internalization or recycling of surface proteins. Moreover, AGS3 overexpression and siRNA-mediated knockdown of AGS3 both result in the dispersal of two endogenously expressed trans-Golgi network (TGN)-associated cargo proteins without influencing those in the cis- or medial-Golgi compartments. Finally, adding a TGN-localization signal to a CD4-derived reporter renders the trafficking of fusion protein sensitive to AGS3. Taken together, our data support a model wherein AGS3 modulates the protein trafficking along the TGN/plasma membrane/endosome loop.
机译：G蛋白信号转导因子3（AGS3）最初在功能性筛选中针对激活异源三聚体G蛋白信号转导的哺乳动物蛋白而鉴定，已知与药物寻找行为有关，在动物模型中可卡因戒断过程中被上调。这些观察结果表明AGS3在神经可塑性形成或维持中的潜在作用。我们已经发现，AGS3的过表达改变了异源表达的质膜受体和通道的一个子集的表面与总比率。通过基于生物素的内化测定法进一步分析一种蛋白质的内吞运输，表明AGS3的过表达适度影响表面蛋白质的内化或再循环。此外，AGS3的过表达和siRNA介导的AGS3的敲低都导致两个内源性表达的反式高尔基体网络（TGN）相关的货物蛋白的分散，而不会影响顺式或中间高尔基体中的蛋白。最后，将TGN定位信号添加到CD4衍生的报告基因使融合蛋白对AGS3敏感。两者合计，我们的数据支持一个模型，其中AGS3调节沿TGN /质膜/内体环的蛋白质运输。

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