Endoplasmic Reticulum Calcium Pumps and Cancer Cell Differentiation

Papp, Béla; Brouland, Jean‐Philippe; Arbabian, Atousa; Gélébart, Pascal; Kovàcs, Tündé; Bobe, Régis; Enouf, Jocelyne; Varin‐Blank, Nadine; Apáti, Ágota

doi:10.3390/biom2010165

Cited by 55 publications

(77 citation statements)

References 136 publications

(174 reference statements)

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“…This may be due to a difference in Ca 2+ influx. Calcium release from the ER combined with capacitative calcium influx from the extracellular space leads to markedly increased cytosolic calcium levels and is involved in cell activation [54] to control key cell-fate processes, which include fertilization, early embryogenesis [55], and differentiation [56]. The amplitude and duration of the Ca 2+ response are decoded by downstream effectors to specify cell fates [57].…”

Section: Discussionmentioning

confidence: 99%

Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

et al. 2016

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BackgroundA fundamental issue in bioscience is to understand the mechanism that underlies the dynamic control of genome-wide expression through the complex temporal-spatial self-organization of the genome to regulate the change in cell fate. We address this issue by elucidating a physically motivated mechanism of self-organization.Principal FindingsBuilding upon transcriptome experimental data for seven distinct cell fates, including early embryonic development, we demonstrate that self-organized criticality (SOC) plays an essential role in the dynamic control of global gene expression regulation at both the population and single-cell levels. The novel findings are as follows: i) Mechanism of cell-fate changes: A sandpile-type critical transition self-organizes overall expression into a few transcription response domains (critical states). A cell-fate change occurs by means of a dissipative pulse-like global perturbation in self-organization through the erasure of initial-state critical behaviors (criticality). Most notably, the reprogramming of early embryo cells destroys the zygote SOC control to initiate self-organization in the new embryonal genome, which passes through a stochastic overall expression pattern. ii) Mechanism of perturbation of SOC controls: Global perturbations in self-organization involve the temporal regulation of critical states. Quantitative evaluation of this perturbation in terminal cell fates reveals that dynamic interactions between critical states determine the critical-state coherent regulation. The occurrence of a temporal change in criticality perturbs this between-states interaction, which directly affects the entire genomic system. Surprisingly, a sub-critical state, corresponding to an ensemble of genes that shows only marginal changes in expression and consequently are considered to be devoid of any interest, plays an essential role in generating a global perturbation in self-organization directed toward the cell-fate change.Conclusion and Significance‘Whole-genome’ regulation of gene expression through self-regulatory SOC control complements gene-by-gene fine tuning and represents a still largely unexplored non-equilibrium statistical mechanism that is responsible for the massive reprogramming of genome expression.

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Section: Discussionmentioning

confidence: 99%

Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

et al. 2016

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“…The SR serve as a storage as well as a source for intracellular Ca 2+ , thus playing a central role in Ca 2+ homeostasis, 1 signaling, 2–4 development of epithelial junctions, 5 cell differentiation, 6 and muscle contractility. 7 Ca 2+ is released from the SR to the cytosol through a variety of receptor/channels such as the ryanodine receptor (RyR), 8 the IP3 receptor, 9 and leak channels.…”

Section: Introductionmentioning

confidence: 99%

The Ca²⁺-ATPase pump facilitates bidirectional proton transport across the sarco/endoplasmic reticulum

Espinoza-Fonseca

2017

Mol. BioSyst.

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Ca2+ transport across the sarco/endoplasmic plasmic reticulum (SR) plays an essential role in intracellular Ca2+ homeostasis, signalling, cell differentiation and muscle contractility. During SR Ca2+ uptake and release, proton fluxes are required to balance the charge deficit generated by exchange of Ca2+ and other ions across the SR. During Ca2+ uptake by the SR Ca2+-ATPase (SERCA), two protons are counter transported from the SR lumen to the cytosol, thus partially compensating for the charge moved by Ca2+ transport. Studies have shown that protons are also transported from the cytosol to the lumen during Ca2+ release, but a transporter that facilitates proton transport into the SR lumen has not been described. In this article we propose that SERCA contains the pathways that facilitate bidirectional proton transport across the SR. We describe the location and structure of water-filled pores in SERCA that form cytosolic and luminal pathways for protons to cross the SR membrane. Based on this structural information, we suggest mechanistic models for proton translocation to the cytosol during active Ca2+ transport, and into the SR lumen during SERCA inhibition by endogenous regulatory proteins. Finally, we discuss the physiological consequences of SERCA-mediated bidirectional proton transport across the SR membrane of muscle and non-muscle cells.

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“…Knockout of SERCA3 significantly impairs endothelium-dependent relaxation of vascular smooth muscle [50], likely associated with impaired activation of nitric oxide synthase. SERCA3 levels are induced during differentiation of various cell types, and in cancer cells SERCA3 displays a complex pattern of up- and downregulation during cell differentiation and at various stages of cancer [51]. This pattern of up- and downregulation is sufficiently distinct that SERCA3 expression has been suggested as a tumor marker to evaluate the progression of cancer [52].…”

Section: Discussionmentioning

confidence: 99%

“…This pattern of up- and downregulation is sufficiently distinct that SERCA3 expression has been suggested as a tumor marker to evaluate the progression of cancer [52]. An important distinction can be made between SERCA2- and SERCA3-associated storage of calcium [51, 53]. For example, in control HL-60 cells SERCA-dependent calcium uptake proceeds ca.…”

Section: Discussionmentioning

confidence: 99%

Inhibition and conformational change of SERCA3b induced by Bcl-2

Hewarathna

Dremina

Schöneich

2017

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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An interaction of Bcl-2 with SERCA had been documented in vitro using the SERCA1a isoform isolated from rat skeletal muscle [Dremina, E. S., Sharov, V. S., Kumar, K., Azidi, A., Michaelis, E. K., Schöneich, C. (2004) Biochem. J. 383 (361–370)]. Here, we demonstrate the interaction of Bcl-2 with the SERCA3b isoform both in vitro and in cell culture. In vitro, the interaction of Bcl-2 with SERCA3b was studied using Bcl-2Δ21, a truncated form of human Bcl-2, and microsomes isolated from SERCA3b-overexpressing HEK-293 cells. For these experiments, SERCA3b was quantified by a combination of amino acid analysis and Western blotting. We observed that Bcl-2Δ21 both inactivates SERCA3b and co-immunoprecipitates with SERCA3b. The incubation with Bcl-2Δ21 changes the distribution of SERCA3b during sucrose density gradient centrifugation, likely as the result of Bcl-2Δ21-induced conformational change of SERCA3b. When SERCA3b-overexpressing HEK-293 cells were co-transfected with Bcl-2, Bcl-2-dependent SERCA3b inactivation was observed. In these cells, Bcl-2 interaction with SERCA3b was demonstrated by co-immunoprecipitation. Furthermore, overexpression of Bcl-2 reduced fluorescein isothiocyanate (FITC) labeling of SERCA3b. Together, our data provide evidence for the interaction of Bcl-2 with SERCA3b in vitro and in cell culture, and for Bcl-2-dependent conformational and functional changes of SERCA3b.

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Endoplasmic Reticulum Calcium Pumps and Cancer Cell Differentiation

Cited by 55 publications

References 136 publications

Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

The Ca²⁺-ATPase pump facilitates bidirectional proton transport across the sarco/endoplasmic reticulum

Inhibition and conformational change of SERCA3b induced by Bcl-2

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Endoplasmic Reticulum Calcium Pumps and Cancer Cell Differentiation

Cited by 55 publications

References 136 publications

Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

The Ca2+-ATPase pump facilitates bidirectional proton transport across the sarco/endoplasmic reticulum

Inhibition and conformational change of SERCA3b induced by Bcl-2

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The Ca²⁺-ATPase pump facilitates bidirectional proton transport across the sarco/endoplasmic reticulum