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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wang, Yixuan Waugh, Richard E. Wan, Jiandi Zhou, Sitong Decourcey, James Cinar, Eyup |
| Description | Author Affiliation: Cinar E ( Microsystems Engineering, Rochester Institute of Technology, Rochester, NY 14623); Zhou S ( Microsystems Engineering, Rochester Institute of Technology, Rochester, NY 14623); DeCourcey J ( Department of Biology, Rochester Institute of Technology, Rochester, NY 14623); Wang Y ( Microsystems Engineering, Rochester Institute of Technology, Rochester, NY 14623); Waugh RE ( Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627.); Wan J ( Microsystems Engineering, Rochester Institute of Technology, Rochester, NY 14623); |
| Abstract | Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced calcium $(Ca^{2+})$ influx. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and $Ca^{2+}$ influx decrease significantly. Remarkably, a critical extracellular $Ca^{2+}$ concentration is required to trigger significant ATP release, but membrane-associated ATP pools in RBCs also contribute to the release of ATP. Our results show how Piezo1 channels are likely to function in normal RBCs and suggest a previously unidentified mechanotransductive pathway in ATP release. Thus, we anticipate that the study will impact broadly on the research of red cells, cellular mechanosensing, and clinical studies related to red cell disorders and vascular disease. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 38 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adenosine Triphosphate Secretion Erythrocytes Ion Channels Metabolism Mechanotransduction, Cellular Calcium Calibration Erythrocyte Membrane Extracellular Space Microfluidics Models, Biological Shear Strength Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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