PIEZO1, sensing the touch during erythropoiesis

Abstract

Purpose of reviewAwarding the 2021 Nobel to Ardem Patapoutian for the discovery of the PIEZO mechanotransducers has emphasized the importance of touch-sensing mechanisms in cell physiology. It is well known that PIEZO1 is expressed at the surface of red blood cells where it adjusts their hydration status under mechanical constraints. Besides this, recent findings suggest that PIEZO1 plays a broader role in erythroid lineage. This review aims to actualize the knowledge on PIEZO1 functions all along erythropoiesis.Recent findingsPIEZO1 is expressed in erythroid progenitors, and controls proliferation and differentiation of nucleated cells, as well as maturation of reticulocytes. As PIEZO1 detects displacements in the range of cell–cell interactions, it might mediate the interaction between the differentiating cells and their microenvironment through an inside-out activation of integrins on human erythroblasts as suggested by in-vitro data. Moreover, PIEZO1 is also expressed at the surface of macrophages where it regulates red blood cells clearance through erythrophagocytosis.SummaryThese new findings on PIEZO1 suggest a continuous effect of mechanotransduction all over erythropoiesis from progenitors to clearance of red blood cells. Therefore, they open a new era in the understanding of hereditary xerocytosis pathophysiology, helping identify new potential therapeutic targets for the future.

Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration

“…In DHSt, PIEZO1 mutations keep the channel in an open conformation with prolonged activity, resulting in Ca 2+ influx and consequent K + efflux though Ca-sensitive Gardos channels, decreasing intracellular osmolarity and causing dehydration of RBCs. 40 , 41 Although the role of TMEM63B in RBCs remains to be elucidated, it is known to be expressed in the RBC membrane ( http://rbcc.hegelab.org/ ), such as PIEZO1 , and might act similarly.…”

Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration

“…In some patients with DHSt, hematologic abnormalities are subtle (35, 36), as also seen in most of our patients in whom they were revealed. In DHSt, PIEZO1 mutations keep the channel in an open conformation with prolonged activity, resulting in Ca 2+ influx and consequent K + efflux though Ca-sensitive Gardos channels, decreasing intracellular osmolarity and causing dehydration of RBCs (36, 37). Although the role of TMEM63B in RBCs remains to be elucidated, it is known to be expressed in the RBC membrane (http://rbcc.hegelab.org/) like PIEZO1 and might act similarly.…”

PIEZO Ion Channels in Cardiovascular Functions and Diseases

“…Myelodysplastic features, including symptomatic anemia, have been reported in humans displaying PIEZO1 mutations. 139 PIEZO1 is expressed in early progenitor cells, and its chemical activation delays erythroblastic and reticulocyte maturation. 140,141 Of note, PIEZO1 GOF mutations linked to DHS induce maturation impairments of RBCs.…”