Actin Cytoskeleton: A Signaling Sensor in Cell Volume Regulation

Papakonstanti, Evangelia A.; Vardaki, Eleftheria; Stournaras, Christos

doi:10.1159/000016366

Cited by 79 publications

(50 citation statements)

References 38 publications

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“…The strong adhesive state is characteristic of a differentiated, quiescent cell, whereas cells in the intermediate adhesive state include those involved in responding to injury during wound healing or tissue remodelling (20). Cell shape can regulate cell fate and function (21) and actin cytoskeleton is critical for cell volume (22). In the present study, we found that Id1 protein could induce cell adhesion and spreading.…”

Section: Discussionsupporting

confidence: 48%

Id1 induces tubulogenesis by regulating endothelial cell adhesion and cytoskeletal organization through β1-integrin and Rho-kinase signalling

Qiu

Wang

Qin³

et al. 2011

Int J Mol Med

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Abstract. The inhibitor of differentiation 1 (Id1) protein is required for tubulogenesis, but the molecular signalling pathways remain unclear. Overexpression (Id1-t) or downregulation (si-Id1) of Id-1 in cell lines, were used to study the function of Id1. The expression of Id1 and β1-integrin was assessed by Western blotting. Up-regulation of Id1 in human umbilical vascular endothelial cells (HUVECs) activated the expression of β1-integrin and promoted cell adhesion and spreading. Conversely, down-regulation of Id1 suppressed β1-integrin expression and inhibited tubulogenesis. By using a β1-integrin antibody to inhibit β1-integrin function, we demonstrated that Id1-induced cell adhesion and tubulogenesis were mediated by β1-integrin. In addition, HUVECs overexpressing Id1 were able to promote capillary tube formation through cytoskeleton reorganization and cell contraction. Finally, the Rho-kinase inhibitor Y27632 inhibited tubulogenesis induced by Id1. Our findings provide evidence that Id1 regulates tubulogenesis in vitro through β1-integrin and Rho-kinase signalling. IntroductionControlled angiogenesis is vital for normal organ development and tissue repair, while angiogenesis can sustain tumorigenesis and age-related macular degeneration (1). In addition, angiogenesis is a key event in the pathogenesis of some forms of cardiovascular disease (2). Although angiogenesis has been identified as a key development in many progressive diseases, the specific molecular mechanisms of angiogenesis are not well understood.The four Id (inhibitor of differentiation or DNA binding) proteins (Id1-4) all contain a helix-loop-helix motif that inhibits the activity of basic helix-loop-helix transcription factors by restraining DNA binding. The Id1 protein has been implicated in the regulation of the cell cycle and in differentiation (3). Since the initial discovery that Id1 is required for angiogenesis (4), Id1 protein induced-angiogenesis has been studied in several experimental systems. Transplantation of mature endothelial cells overexpressing Id1 may serve as a novel and useful strategy for therapeutic angiogenesis (5). Studies have also indicated that the overexpression of Id1 protein was correlated with angiogenesis in tumors (6). Although the molecular mechanisms of Id1-mediated cell proliferation and apoptosis have been identified (7), little is known about the mechanism of Id1-mediated angiogenesis.Angiogenesis is a complex event and requires a wellorchestrated integration of migration, proliferation, extracellular matrix (ECM) degradation, cell contraction, and survival. Previous studies reported that Id1 can regulate cell migration (5), proliferation (5) and ECM degradation (8). However, cellmatrix adhesion and F-actin cytoskeleton reorganization, which play crucial roles in endothelial cell adhesion during angiogenesis (9,10), were absent. Moreover, cytoskeletal regulatory molecules are probably involved in angiogenesis (11). Furthermore, angiogenesis requires a polarized morphology with a single, broad lamellipod...

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Section: Discussionsupporting

confidence: 48%

Id1 induces tubulogenesis by regulating endothelial cell adhesion and cytoskeletal organization through β1-integrin and Rho-kinase signalling

Qiu

Wang

Qin³

et al. 2011

Int J Mol Med

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“…Despite this swelling of cells, other well defined characteristics of apoptosis including chromatin condensation, externalization of the phosphatidylserine, caspase activity, and DNA degradation persisted. Furthermore, maintenance of normal physiologic intracellular ion concentrations has been shown to inhibit caspase activation and apoptotic nuclease activity during programmed cell death (14 -17).The actin cytoskeleton is well recognized to regulate the activity of ion channels and transporters involved in maintaining cellular homeostasis and cell volume (18,19). The importance of ion redistribution during apoptosis has, thus, led us to consider the potential role of the actin cytoskeleton in the cell death program during AVD.…”

mentioning

confidence: 99%

“…The actin cytoskeleton is well recognized to regulate the activity of ion channels and transporters involved in maintaining cellular homeostasis and cell volume (18,19). The importance of ion redistribution during apoptosis has, thus, led us to consider the potential role of the actin cytoskeleton in the cell death program during AVD.…”

mentioning

confidence: 99%

Cationic Gradient Reversal and Cytoskeleton-independent Volume Regulatory Pathways Define an Early Stage of Apoptosis

Bortner

Sifre

Cidlowski

2008

Journal of Biological Chemistry

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Cell shrinkage, or apoptotic volume decrease (AVD), is a ubiquitous characteristic of programmed cell death that is independent of the death stimulus and occurs in all examples of apoptosis. Here we distinguished two specific stages of AVD based on cell size and a unique early reversal of intracellular ions that occurs in response to activation of both intrinsic and extrinsic cell death signal pathways. The primary stage of AVD is characterized by an early exchange of the normal intracellular ion distribution for sodium from 12 to 113.6 mM and potassium from 139.5 to 30 mM. This early ionic reversal is associated with a 20 -40% decrease in cell volume, externalization of phosphatidylserine, loss of mitochondrial membrane potential, and caspase activation and activity along with nuclear condensation that occurs independent of actin cytoskeleton disruption. Disruption of the actin cytoskeleton, however, prevents a secondary stage of AVD in apoptotic cells, characterized by a loss of both potassium and sodium that results in an 80 -85% loss in cell volume, DNA degradation, and apoptotic body formation. Together these studies demonstrate that AVD occurs in two distinct stages with the earliest stage reflecting a cellular cationic gradient reversal.Apoptosis, or programmed cell death, is a fundamental process in which activation of specific biochemical and morphological events results in death. Cell volume loss, chromatin condensation, and internucleosomal DNA fragmentation are all defining characteristics of this mode of cell death (1, 2). Externalization of phosphatidylserine, depolarization of the mitochondrial membrane potential along with release of various mitochondrial components, and caspase activity have also been used to identify apoptosis (3-5). The interplay of these catabolic events in the cell death program in relation to the loss of cell volume is not well understood.Apoptotic volume decrease (AVD 2 (6)) or the loss of cell volume during apoptosis is thought to result primarily from changes in the intracellular ionic environment. The movement of monovalent ions, particularly sodium and potassium, has been shown to play a pivotal role in both the activation and execution of apoptosis (7-9). Loss of intracellular sodium and potassium has been shown to occur in the shrunken population of apoptotic cells as part of AVD (6, 10, 11). However, earlier studies have shown that an increase in intracellular sodium also occurs during apoptosis (12, 13). Studies with sodium-substituted media revealed that sodium influx is a necessary requirement for AVD during apoptosis in cells treated with Fas ligand, since apoptotic stimulation in the absence of extracellular sodium resulted in cellular swelling rather than shrinkage (13). Despite this swelling of cells, other well defined characteristics of apoptosis including chromatin condensation, externalization of the phosphatidylserine, caspase activity, and DNA degradation persisted. Furthermore, maintenance of normal physiologic intracellular ion concentrations has been...

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“…The response cascade can be classified into four mechanistic components: volume sensing, signal generation, signal transduction, and effector activation (10). Given that PIP 2 is a multifunctional regulator and adaptor, the PIP 2 increase may coordinate many of the responses to hypertonic stress.…”

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confidence: 99%

Hypertonic Stress Increases Phosphatidylinositol 4,5-Bisphosphate Levels by Activating PIP5KIβ

Yamamoto¹,

Chen²,

Wang

et al. 2006

Journal of Biological Chemistry

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2 and actin cytoskeletal responses. PIP5KI␤ was recruited to membranes and was activated by hypertonic stress through Ser/ Thr dephosphorylation. Calyculin A, a protein phosphatase 1 inhibitor, blocked the hypertonicity-induced PIP5KI␤ dephosphorylation/activation as well as PIP 2 increase in cells. Urea, which raises osmolarity without inducing cell shrinkage, did not promote dephosphorylation nor increase PIP 2 levels. Disruption or stabilization of the actin cytoskeleton, or inhibition of the Rho kinase, did not block the PIP 2 increase nor PIP5KI␤ dephosphorylation. Therefore, PIP5KI␤ is dephosphorylated in a volume-dependent manner by a calyculin A-sensitive protein phosphatase, which is activated upstream of actin remodeling and independently of Rho kinase activation. Our results establish a cause-and-effect relation between PIP5KI␤ dephosphorylation, lipid kinase activation, and PIP 2 increase in cells. This PIP 2 increase can orchestrate multiple downstream responses, including the reorganization of the actin cytoskeleton.All cells experience fluctuations in osmolarity. Unicellular organisms and plants continuously confront osmotic challenges in their environment. In higher animals, the kidney and the gastrointestinal system are routinely exposed to severe osmotic fluctuation, while the majority of cells in other organs are protected from large tonicity changes. Nevertheless, these other organs are also confronted with transient osmolarity variations due to changes in the transmembrane transport of solutes or shifts in the balance between low molecular weight precursors and their macromolecular products. Recently, there has been a renewed interest in understanding the mechanism of hypertonic response in the clinical arena (1), due to the discovery that treatments using hypertonic resuscitation in experimental models of trauma, hemorrhagic shock, sepsis, and burn injury are more beneficial than conventional isotonic resuscitation (2, 3). While the fundamental mechanism for such protection is not completely understood, the actin cytoskeleton, which is reorganized during hypertonic stress, has been implicated (3, 4).Actin remodeling as well as many of the other hyperosmotic responses are evolutionary conserved. These include large shifts in phosphoinositide metabolism, activation of the mitogen-activated protein and tyrosine kinase pathways, volume regulation and the reprogramming of gene transcription (3, 5). Phosphatidylinositol 4-phosphate (PI4P) 4 and phosphatidylinositol 4,5-bisphosphate (PIP 2 ) levels increase dramatically in mammalian cardiac muscle and tissue culture cells that were exposed to hypertonic sucrose or NaCl (6). Other phosphoinositides, including phosphatidylinositol 3,5-bisphosphate (7, 8), phosphatidylinositol 3,4-bisphosphate, and phosphatidylinositol 3,4,5-trisphosphate are increased in some other types of cells as well (9).Hyperosmotic stress acutely induces cell shrinkage, which is subsequently corrected by volume regulation. The response cascade can be classified into four mecha...

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Actin Cytoskeleton: A Signaling Sensor in Cell Volume Regulation

Cited by 79 publications

References 38 publications

Id1 induces tubulogenesis by regulating endothelial cell adhesion and cytoskeletal organization through β1-integrin and Rho-kinase signalling

Id1 induces tubulogenesis by regulating endothelial cell adhesion and cytoskeletal organization through β1-integrin and Rho-kinase signalling

Cationic Gradient Reversal and Cytoskeleton-independent Volume Regulatory Pathways Define an Early Stage of Apoptosis

Hypertonic Stress Increases Phosphatidylinositol 4,5-Bisphosphate Levels by Activating PIP5KIβ

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