Hyperpolarization of the plasma membrane potential provokes reorganization of the actin cytoskeleton and increases the stability of adherens junctions in bovine corneal endothelial cells in culture

Nin, Verónica; Hernández, Julio A.; Chifflet, Silvia

doi:10.1002/cm.20416

Cited by 29 publications

(34 citation statements)

References 63 publications

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“…45,94 The cytoskeleton has also been identified by microarray analysis as a possible mediator of the depolarization response. This is supported by previous work demonstrating that V mem depolarization and hyperpolarization affect actin and tubulin cytoskeleton organization [95][96][97] and that ion transport proteins and cytoskeletal proteins can interact directly to regulate each other's functions. 98-100 GSEA also implicated mRNA processing and protein degradation, both of which have been shown to be regulated by depolarization in neurons.…”

Section: Discussionsupporting

confidence: 75%

Depolarization Alters Phenotype, Maintains Plasticity of Predifferentiated Mesenchymal Stem Cells

Sundelacruz

Levin²,

Kaplan³

2013

Tissue Engineering Part A

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Although adult stem cell transplantation has been implemented as a therapy for tissue repair, it is limited by the availability of functional adult stem cells. A potential approach to generate stem and progenitor cells may be to modulate the differentiated status of somatic cells. Therefore, there is a need for a better understanding of how the differentiated phenotype of mature cells is regulated. We hypothesize that bioelectric signaling plays an important role in the maintenance of the differentiated state, as it is a functional regulator of the differentiation process in various cells and tissues. In this study, we asked whether the mature phenotype of osteoblasts and adipocytes derived from human mesenchymal stem cells (hMSCs) could be altered by modulation of their membrane potential. hMSC-derived osteoblasts and adipocytes were depolarized by treatment with ouabain, a Na(+)/K(+) ATPase inhibitor, or by treatment with high concentrations of extracellular K(+). To characterize the effect of voltage modulation on the differentiated state, the depolarized cells were evaluated for (1) the loss of differentiation markers; (2) the up-regulation of stemness markers and stem properties; and (3) differences in gene expression profiles in response to voltage modulation. hMSC-derived osteoblasts and adipocytes exhibited significant down-regulation of bone and fat tissue markers in response to depolarization, despite the presence of differentiation-inducing soluble factors, suggesting that bioelectric signaling overrides biochemical signaling in the maintenance of cell state. Suppression of the osteoblast or adipocyte phenotype was not accompanied by up-regulation of genes associated with the stem state. Thus, depolarization does not activate the stem cell genetic signature and, therefore, does not induce a full reprogramming event. However, after transdifferentiating the depolarized cells to evaluate for multi-lineage potential, depolarized osteoblasts demonstrated improved ability to achieve correct adipocyte morphology compared with nondepolarized osteoblasts. The present study thus demonstrates that depolarization reduces the differentiated phenotype of hMSC-derived cells and improves their transdifferentiation capacity, but does not restore a stem-like genetic profile. Through global transcript profiling of depolarized osteoblasts, we identified pathways that may mediate the effects of voltage signaling on cell state, which will require a detailed mechanistic inquiry in future studies.

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Section: Discussionsupporting

confidence: 75%

Depolarization Alters Phenotype, Maintains Plasticity of Predifferentiated Mesenchymal Stem Cells

Sundelacruz

Levin²,

Kaplan³

2013

Tissue Engineering Part A

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“…In MDCK cells, Vaaraniemi et al [126] found that activation of protein kinase C determined PMP depolarization and reorganization of the spectrin-based and actin cytoskeletons. Consistently with these findings, we showed that the nonspecific modifications of the PMP (i.e., depolarization or hyperpolarization) promote changes in the organization of the actin and tubulin cytoskeletons in bovine corneal endothelial (BCE) cells in culture [127, 128]. In particular, the changes observed for the actin cytoskeleton consisted, for the PMP depolarization, in a gradual loss of the peripheral ring, an increase in F-actin throughout the cytoplasm, appearance of intercellular gaps and, for sufficiently prolonged treatments, eventual cell detachment [127].…”

Section: Modulation Of the Epithelial Actin Cytoskeleton By Modifisupporting

confidence: 54%

The Plasma Membrane Potential and the Organization of the Actin Cytoskeleton of Epithelial Cells

Chifflet

Hernández

2012

International Journal of Cell Biology

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The establishment and maintenance of the polarized epithelial phenotype require a characteristic organization of the cytoskeletal components. There are many cellular effectors involved in the regulation of the cytoskeleton of epithelial cells. Recently, modifications in the plasma membrane potential (PMP) have been suggested to participate in the modulation of the cytoskeletal organization of epithelia. Here, we review evidence showing that changes in the PMP of diverse epithelial cells promote characteristic modifications in the cytoskeletal organization, with a focus on the actin cytoskeleton. The molecular paths mediating these effects may include voltage-sensitive integral membrane proteins and/or peripheral proteins sensitive to surface potentials. The voltage dependence of the cytoskeletal organization seems to have implications in several physiological processes, including epithelial wound healing and apoptosis.

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Section: Discussionsupporting

confidence: 75%

Depolarization alters phenotype, maintains plasticity of pre-differentiated mesenchymal stem cells

Sundelacruz¹,

Levin²,

Kaplan³

2013

Tissue Engineering Part A

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Although adult stem cell transplantation has been implemented as a therapy for tissue repair, it is limited by the availability of functional adult stem cells. A potential approach to generate stem and progenitor cells may be to modulate the differentiated status of somatic cells. Therefore, there is a need for a better understanding of how the differentiated phenotype of mature cells is regulated. We hypothesize that bioelectric signaling plays an important role in the maintenance of the differentiated state, as it is a functional regulator of the differentiation process in various cells and tissues. In this study, we asked whether the mature phenotype of osteoblasts and adipocytes derived from human mesenchymal stem cells (hMSCs) could be altered by modulation of their membrane potential. hMSC-derived osteoblasts and adipocytes were depolarized by treatment with ouabain, a Na + /K + ATPase inhibitor, or by treatment with high concentrations of extracellular K + . To characterize the effect of voltage modulation on the differentiated state, the depolarized cells were evaluated for (1) the loss of differentiation markers; (2) the up-regulation of stemness markers and stem properties; and (3) differences in gene expression profiles in response to voltage modulation. hMSC-derived osteoblasts and adipocytes exhibited significant down-regulation of bone and fat tissue markers in response to depolarization, despite the presence of differentiation-inducing soluble factors, suggesting that bioelectric signaling overrides biochemical signaling in the maintenance of cell state. Suppression of the osteoblast or adipocyte phenotype was not accompanied by upregulation of genes associated with the stem state. Thus, depolarization does not activate the stem cell genetic signature and, therefore, does not induce a full reprogramming event. However, after transdifferentiating the depolarized cells to evaluate for multi-lineage potential, depolarized osteoblasts demonstrated improved ability to achieve correct adipocyte morphology compared with nondepolarized osteoblasts. The present study thus demonstrates that depolarization reduces the differentiated phenotype of hMSC-derived cells and improves their transdifferentiation capacity, but does not restore a stem-like genetic profile. Through global transcript profiling of depolarized osteoblasts, we identified pathways that may mediate the effects of voltage signaling on cell state, which will require a detailed mechanistic inquiry in future studies.

show abstract

Hyperpolarization of the plasma membrane potential provokes reorganization of the actin cytoskeleton and increases the stability of adherens junctions in bovine corneal endothelial cells in culture

Cited by 29 publications

References 63 publications

Depolarization Alters Phenotype, Maintains Plasticity of Predifferentiated Mesenchymal Stem Cells

Depolarization Alters Phenotype, Maintains Plasticity of Predifferentiated Mesenchymal Stem Cells

The Plasma Membrane Potential and the Organization of the Actin Cytoskeleton of Epithelial Cells

Depolarization alters phenotype, maintains plasticity of pre-differentiated mesenchymal stem cells

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