2023-08-21 インペリアル・カレッジ・ロンドン(ICL)
◆これにより、さまざまな疾患の新たな薬物標的の可能性が示唆され、特にがん治療において重要な役割を果たす可能性があります。Piezoチャネルは血圧、呼吸、膀胱の制御、免疫システムなど、体内の様々なプロセスを調整する重要な役割を果たしており、がんを含む疾患の将来的な薬物標的となる可能性があります。
◆Piezo1活性を視覚化するための新たな方法を開発し、これによりこれらのチャネルの役割を詳細に理解することが可能になりました。
<関連情報>
- https://www.imperial.ac.uk/news/247074/nobel-winning-bodily-pressure-sensors-filmed-first/
- https://www.nature.com/articles/s41467-023-40134-y
GenEPiを用いたピエゾ1依存性活動の高特異的かつ非侵襲的なイメージング Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi
Sine Yaganoglu,Konstantinos Kalyviotis,Christina Vagena-Pantoula,Dörthe Jülich,Benjamin M. Gaub,Maaike Welling,Tatiana Lopes,Dariusz Lachowski,See Swee Tang,Armando Del Rio Hernandez,Victoria Salem,Daniel J. Müller,Scott A. Holley,Julien Vermot,Jian Shi,Nordine Helassa,Katalin Török & Periklis Pantazis
Nature Communications Published:19 July 2023
DOI:https://doi.org/10.1038/s41467-023-40134-y
Abstract
Mechanosensing is a ubiquitous process to translate external mechanical stimuli into biological responses. Piezo1 ion channels are directly gated by mechanical forces and play an essential role in cellular mechanotransduction. However, readouts of Piezo1 activity are mainly examined by invasive or indirect techniques, such as electrophysiological analyses and cytosolic calcium imaging. Here, we introduce GenEPi, a genetically-encoded fluorescent reporter for non-invasive optical monitoring of Piezo1-dependent activity. We demonstrate that GenEPi has high spatiotemporal resolution for Piezo1-dependent stimuli from the single-cell level to that of the entire organism. GenEPi reveals transient, local mechanical stimuli in the plasma membrane of single cells, resolves repetitive contraction-triggered stimulation of beating cardiomyocytes within microtissues, and allows for robust and reliable monitoring of Piezo1-dependent activity in vivo. GenEPi will enable non-invasive optical monitoring of Piezo1 activity in mechanochemical feedback loops during development, homeostatic regulation, and disease.
