The team led by Professor Liu Bo from the School of Biomedical Engineering at our university has been dedicated to the design and application of biological probes based on Fluorescence Resonance Energy Transfer (FRET) technology in recent years. After achieving the first visualization study of cell membrane surface tension and publishing the results in the iScience sub-journal of Cell in September 2018, Professor Liu Bo's team made another breakthrough in the study of the live-cell RhoGDIα protein activity detection probe based on FRET. The recent research results were accepted and published online by the magazine Communications Biology under Nature (full text link).
Changes in cell polarity are prerequisites for diseases such as tumor metastasis. The Rho protein family, which plays a crucial role in forming cell polarity, is regulated by Rho GDP dissociation inhibitor α (RhoGDIα). However, the academic community has always believed that the activity of the RhoGDIα protein is only regulated by the Rho protein family. Due to the lack of effective tools to observe its activity in living cells in real-time, the activity distribution of RhoGDIα protein in cells has never been detected. To address this issue, Professor Liu Bo's team from our school utilized FRET technology and successfully constructed a sl-RhoGDIα biological probe that can dynamically detect RhoGDIα activity changes in live cells. They further applied this probe for an in-depth study of the polarity changes of tumor cells under shear stress. The results for the first time show that external shear stress leads to uneven distribution of cell membrane fluidity, transmitting stress from the outside of the cell to the inside, and propagating it along the filaments connected to the cell membrane. This process activates the Src protein on the filaments to phosphorylate RhoGDIα through its polarization stress sensor. This discovery process has changed the long-standing viewpoint in the academic world, indicating that the activity regulation pathways of RhoGDIα and the Rho protein family are relatively independent, and there is no direct connection between the two.
Schematic diagram of shear stress activating RhoGDIα and the sl-RhoGDIα probe.
The research was funded by the National Natural Science Foundation (No. 31670867, 31670961, 11532004). The co-first authors of the paper are former graduate student Shao Shuai from DUT’s School of Biomedical Engineering (currently a doctoral student in the Department of Information Technology at the University of Oulu, Finland) and Professor Liao Xiaoling from Chongqing University of Science and Technology. Professor Liu Bo is the corresponding author of the paper.
Communications Biology is a newly launched open-access journal under Nature, focusing on cutting-edge research in the life sciences field.
