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Spatiotemporal Control of TGF-β Signaling with Light
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-01-12 00:00:00 , DOI: 10.1021/acssynbio.7b00225
Yuchao Li 1 , Minji Lee 2 , Nury Kim 3 , Guoyu Wu 1 , Difan Deng 1 , Jin Man Kim 2 , Xuedong Liu 4 , Won Do Heo 2, 3, 5 , Zhike Zi 1
Affiliation  

Cells employ signaling pathways to make decisions in response to changes in their immediate environment. Transforming growth factor beta (TGF-β) is an important growth factor that regulates many cellular functions in development and disease. Although the molecular mechanisms of TGF-β signaling have been well studied, our understanding of this pathway is limited by the lack of tools that allow the control of TGF-β signaling with high spatiotemporal resolution. Here, we developed an optogenetic system (optoTGFBRs) that enables the precise control of TGF-β signaling in time and space. Using the optoTGFBRs system, we show that TGF-β signaling can be selectively and sequentially activated in single cells through the modulation of the pattern of light stimulations. By simultaneously monitoring the subcellular localization of TGF-β receptor and Smad2 proteins, we characterized the dynamics of TGF-β signaling in response to different patterns of blue light stimulations. The spatial and temporal precision of light control will make the optoTGFBRs system as a powerful tool for quantitative analyses of TGF-β signaling at the single cell level.

中文翻译:

TGF-β信号光的时空控制

细胞利用信号传导途径做出反应,以响应其周围环境的变化。转化生长因子β(TGF-β)是重要的生长因子,可调节发育和疾病中的许多细胞功能。尽管已经对TGF-β信号转导的分子机制进行了深入研究,但由于缺乏可用于以高时空分辨率控制TGF-β信号转导的工具,我们对这一途径的理解受到限制。在这里,我们开发了一种光遗传系统(optoTGFBRs),它可以在时间和空间上精确控制TGF-β信号传导。使用optoTGFBRs系统,我们显示TGF-β信号传导可以通过光刺激模式的调制在单个细胞中选择性地和顺序地激活。通过同时监测TGF-β受体和Smad2蛋白的亚细胞定位,我们表征了响应不同模式的蓝光刺激的TGF-β信号传导的动力学。光控制的时空精度将使optoTGFBRs系统成为在单细胞水平上定量分析TGF-β信号的强大工具。
更新日期:2018-01-12
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