Piezo1 regulates mechanotransductive release of ATP from human RBCs


ÇİNAR E., Zhou S., DeCourcey J., Wang Y., Waugh R. E., Wan J.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, cilt.112, sa.38, ss.11783-11788, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 112 Sayı: 38
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1073/pnas.1507309112
  • Dergi Adı: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.11783-11788
  • Anahtar Kelimeler: Pizeo1, mechanosensing, ATP release, calcium flux, RBCs, RED-BLOOD-CELLS, DEFORMATION-INDUCED RELEASE, ACTIVATED CATION CHANNELS, VESSELS IN-VIVO, RESISTANCE VESSELS, ION-CHANNEL, MECHANICAL CHANNEL, ENDOTHELIAL-CELLS, CALCIUM-PUMP, ERYTHROCYTES
  • Eskişehir Osmangazi Üniversitesi Adresli: Hayır

Özet

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 (Ca2+) influx. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and Ca2+ influx decrease significantly. Remarkably, a critical extracellular Ca2+ 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.