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Functional plasticity of the N-methyl-D-aspartate receptor in differentiating human erythroid precursor cells


Hanggi, Pascal; Telezhkin, Vsevolod; Kemp, Paul J; Schmugge, Markus; Gassmann, Max; Goede, Jeroen S; Speer, Oliver; Bogdanova, Anna (2015). Functional plasticity of the N-methyl-D-aspartate receptor in differentiating human erythroid precursor cells. American journal of Physiology. Cell physiology, 308(12):C993-C1007.

Abstract

Calcium signaling is essential to support erythroid proliferation and differentiation. Precise control of the intracellular Ca(2+) levels in erythroid precursor cells (EPCs) is afforded by coordinated expression and function of several cation channels, including the recently identified N methyl D aspartate receptor (NMDAR). Here, we characterized the changes in Ca(2+) uptake and electric currents mediated by the NMDARs occurring during EPC differentiation using flow cytometry and patch clamp. During erythropoietic maturation, subunit composition and properties of the receptor changed; in proerythroblasts and basophilic erythroblasts, fast deactivating currents with high amplitudes mediated by the GluN2A subunit-dominated receptors, whilst at the polychromatic and orthochromatic erythroblast stages, the GluN2C subunit was getting more abundant overriding the expression of GluN2A. At these stages, the currents mediated by the NMDARs carried the features characteristic the GluN2C-containing receptors such as prolonged decay time and lower conductance. Kinetics of this switch in the NMDAR properties and abundance varied markedly from donor to donor. Despite this variability, NMDARs were essential for survival of EPC in any subject tested. Our findings indicate that NMDARs have a dual role during erythropoiesis, supporting survival of polychromatic erythroblasts and contributing to the Ca(2+) homeostasis from the orthochromatic erythroblast stage to circulating red blood cells.

Abstract

Calcium signaling is essential to support erythroid proliferation and differentiation. Precise control of the intracellular Ca(2+) levels in erythroid precursor cells (EPCs) is afforded by coordinated expression and function of several cation channels, including the recently identified N methyl D aspartate receptor (NMDAR). Here, we characterized the changes in Ca(2+) uptake and electric currents mediated by the NMDARs occurring during EPC differentiation using flow cytometry and patch clamp. During erythropoietic maturation, subunit composition and properties of the receptor changed; in proerythroblasts and basophilic erythroblasts, fast deactivating currents with high amplitudes mediated by the GluN2A subunit-dominated receptors, whilst at the polychromatic and orthochromatic erythroblast stages, the GluN2C subunit was getting more abundant overriding the expression of GluN2A. At these stages, the currents mediated by the NMDARs carried the features characteristic the GluN2C-containing receptors such as prolonged decay time and lower conductance. Kinetics of this switch in the NMDAR properties and abundance varied markedly from donor to donor. Despite this variability, NMDARs were essential for survival of EPC in any subject tested. Our findings indicate that NMDARs have a dual role during erythropoiesis, supporting survival of polychromatic erythroblasts and contributing to the Ca(2+) homeostasis from the orthochromatic erythroblast stage to circulating red blood cells.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:18 March 2015
Deposited On:15 Apr 2015 13:49
Last Modified:08 Dec 2017 12:48
Publisher:American Physiological Society
ISSN:0363-6143
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1152/ajpcell.00395.2014
PubMed ID:25788577

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