FRET-based monitoring of Adhesion class G protein-coupled receptor activity (C03)

粘附型G蛋白偶联受体(AGPCR)的刺激方式和信号转导事件尚不清楚。以前的工作表明，aGPCRs可能通过细胞外和跨膜受体部分之间的分子内距离变化来感知机械信号。该项目将使用FRET测量来光学量化配体暴露时的这种变化，并在已建立的果蝇模型中测试人工延长的aGPCR变体的受体活性变化。最后，FRET传感器构建将被用来评估人类突变对aGPCR距离变化的影响。

Stimulus modality and signal transduction events of G protein-coupled receptors of the Adhesion class (aGPCR) are poorly defined. Previous work suggests that aGPCRs sense mechanical signals, possibly through intramolecular distance changes between extracellular and transmembrane receptor portions. This project will use FRET measurements to optically quantify such changes upon ligand exposure, and test artificially elongated aGPCR variants for altered receptor activity in an established Drosophila model. Lastly, FRET sensor constructs will be employed to assess the effect of human mutations on aGPCR distance changes.