Piezo1 regulates mechanotransductive release of ATP from human RBCs.
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.
Microsystems Engineering, Rochester Institute of Technology, Rochester, NY 14623;
Eyup
E
Cinar
Microsystems Engineering, Rochester Institute of Technology, Rochester, NY 14623;
Sitong
S
Zhou
Department of Biology, Rochester Institute of Technology, Rochester, NY 14623;
James
J
DeCourcey
Microsystems Engineering, Rochester Institute of Technology, Rochester, NY 14623; School of Mechanical Engineering, University of Science and Technology, Beijing 100083, China;
Yixuan
Y
Wang
Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627.
Richard E
RE
Waugh
Microsystems Engineering, Rochester Institute of Technology, Rochester, NY 14623; jdween@rit.edu.
Jiandi
J
Wan
D000255:Adenosine Triphosphate / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002138:Calibration; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D044085:Microfluidics; D008954:Models, Biological; D033081:Shear Strength
D007473:Ion Channels; C515204:PIEZO1 protein, human; D000255:Adenosine Triphosphate; D002118:Calcium
ATP release; Pizeo1; RBCs; calcium flux; mechanosensing