Neuroscience Program, University of Illinois, Urbana-Champaign, Urbana, IL, 61801, USA.
Convergence Research Center for Diagnosis Treatment Care of Dementia, Korea Institute of Science and Technology (KIST), Seoul, 02792, South Korea.
Sci Rep. 2017 May 9;7(1):1593. doi: 10.1038/s41598-017-01789-y.
Platelet-derived growth factor receptor (PDGFR) senses extracellular growth factors and transfer the signals inside the cells regulating cell proliferation, migration and survival. It has been controversial at which membrane microdomains PDGFRs reside and how they control such diverse intracellular signaling pathways. Here, we developed a novel PDGFR biosensor based on fluorescence resonance energy transfer (FRET), which can detect the real-time PDGFR activity in live cells with high spatiotemporal resolutions. To study subcellular PDGFR activity at membrane microdomains, this PDGFR biosensor was further targeted in or outside lipid rafts via different lipid modification signals. The results suggest that, in response to PDGF stimulation, PDGFR activity is evenly distributed at different membrane microdomains, while integrin-mediated signaling events have inhibitory effects on the activation of PDGFR specifically located in lipid rafts but not outside rafts, implying the role of lipid microdomains as segregated signaling platforms.
血小板衍生生长因子受体（PDGFR）感知细胞外生长因子，并将信号传递到细胞内，调节细胞增殖、迁移和存活。PDGFR 位于哪种膜微区以及它们如何控制如此多样化的细胞内信号通路一直存在争议。在这里，我们开发了一种基于荧光共振能量转移（FRET）的新型 PDGFR 生物传感器，可在活细胞中以高时空分辨率实时检测 PDGFR 活性。为了研究细胞膜微区的亚细胞 PDGFR 活性，该 PDGFR 生物传感器通过不同的脂质修饰信号被靶向到脂质筏内或脂质筏外。结果表明，在 PDGF 刺激下，PDGFR 活性均匀分布在不同的膜微区，而整合素介导的信号事件对位于脂质筏内而非筏外的 PDGFR 的激活具有抑制作用，这表明脂质微区作为分隔的信号平台的作用。
