To shrink or not to shrink

Mohandas, Narla

doi:10.1182/blood-2013-04-491753

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…It has been suggested that Piezo1 plays a previously unrecognized role in erythrocyte volume regulation, with HX erythrocytes gradually becoming dehydrated during repeated cycles of travel through the microcirculation, associated with changes in oxygenation/deoxygenation (34). A potential role in regulating a stretch-activated calcium pathway has also been suggested (35)(36)(37)(38).…”

Section: Piezo1 In Erythrocytesmentioning

confidence: 99%

Piezo Proteins: Regulators of Mechanosensation and Other Cellular Processes

Bagriantsev

Gracheva

Gallagher

2014

Journal of Biological Chemistry

195

174

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Section: Piezo1 In Erythrocytesmentioning

confidence: 99%

Piezo Proteins: Regulators of Mechanosensation and Other Cellular Processes

Bagriantsev

Gracheva

Gallagher

2014

Journal of Biological Chemistry

195

174

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“…It has been suggested that PIEZO1 plays a role in erythrocyte volume regulation, with PIEZO1-mutant HX erythrocytes gradually becoming dehydrated during their repeated cycles of travel through the microcirculation, associated with changes in oxygenation/deoxygenation. 35 Genetic and physiologic studies implicate a role for PIEZO1 in volume homeostasis. Volume sensing, a poorly understood process in vertebrate cells, has been linked to stretchactivated currents induced by changes in cell volume.…”

Section: Piezo1 and Erythrocyte Volumementioning

confidence: 99%

Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis

Glogowska¹,

Schneider

Maksimova³

et al. 2017

Blood

111

118

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Mutations in PIEZO1 are the primary cause of hereditary xerocytosis, a clinically heterogeneous, dominantly inherited disorder of erythrocyte dehydration. We used next-generation sequencing-based techniques to identify mutations in individuals from 9 kindreds referred with suspected hereditary xerocytosis (HX) and/or undiagnosed congenital hemolytic anemia. Mutations were primarily found in the highly conserved, COOH-terminal pore-region domain. Several mutations were novel and demonstrated ethnic specificity. We characterized these mutations using genomic-, bioinformatic-, cell biology-, and physiology-based functional assays. For these studies, we created a novel, cell-based in vivo system for study of wild-type and variant PIEZO1 membrane protein expression, trafficking, and electrophysiology in a rigorous manner. Previous reports have indicated HX-associated PIEZO1 variants exhibit a partial gain-of-function phenotype with generation of mechanically activated currents that inactivate more slowly than wild type, indicating that increased cation permeability may lead to dehydration of PIEZO1-mutant HX erythrocytes. In addition to delayed channel inactivation, we found additional alterations in mutant PIEZO1 channel kinetics, differences in response to osmotic stress, and altered membrane protein trafficking, predicting variant alleles that worsen or ameliorate erythrocyte hydration. These results extend the genetic heterogeneity observed in HX and indicate that various pathophysiologic mechanisms contribute to the HX phenotype.

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“…59 It has been suggested that PIEZO plays a role in erythrocyte volume regulation, 60 with PIEZO1-mutant HX erythrocytes gradually becoming dehydrated during their repeated cycles of travel through the microcirculation, associated with changes in oxygenation/deoxygenation. 61 Volume sensing, a poorly understood process in vertebrate cells, has been linked to stretch-activated currents induced by changes in cell volume. 62 The PIEZO1 blocker, Grammostola spatulata mechanotoxin, inhibits mechanically activated currents and whole cell regulatory volume decreases, indicating a role in volume homeostasis.…”

Section: Dehydrationmentioning

confidence: 99%

Disorders of erythrocyte hydration

Gallagher

2017

Blood

100

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The erythrocyte contains a network of pathways that regulate salt and water content in the face of extracellular and intracellular osmotic perturbations. This allows the erythrocyte to maintain a narrow range of cell hemoglobin concentration, a process critical for normal red blood cell function and survival. Primary disorders that perturb volume homeostasis jeopardize the erythrocyte and may lead to its premature destruction. These disorders are marked by clinical, laboratory, and physiologic heterogeneity. Recent studies have revealed that these disorders are also marked by genetic heterogeneity. They have implicated roles for several proteins, PIEZO1, a mammalian mechanosensory protein; GLUT1, the glucose transporter; SLC4A1, the anion transporter; RhAG, the Rh-associated glycoprotein; KCNN4, the Gardos channel; and ABCB6, an adenosine triphosphate-binding cassette family member, in the maintenance of erythrocyte volume homeostasis. Secondary disorders of erythrocyte hydration include sickle cell disease, thalassemia, hemoglobin CC, and hereditary spherocytosis, where cellular dehydration may be a significant contributor to disease pathology and clinical complications. Understanding the pathways regulating erythrocyte water and solute content may reveal innovative strategies to maintain normal volume in disorders associated with primary or secondary cellular dehydration. These mechanisms will serve as a paradigm for other cells and may reveal new therapeutic targets for disease prevention and treatment beyond the erythrocyte.

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To shrink or not to shrink

Cited by 4 publications

References 9 publications

Piezo Proteins: Regulators of Mechanosensation and Other Cellular Processes

Piezo Proteins: Regulators of Mechanosensation and Other Cellular Processes

Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis

Disorders of erythrocyte hydration

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