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1.
Calcium Signaling-Mediated Plant Response to Cold Stress.
Yuan, P, Yang, T, Poovaiah, BW
International journal of molecular sciences. 2018;(12)
Abstract
Low temperatures have adverse impacts on plant growth, developmental processes, crop productivity and food quality. It is becoming clear that Ca2+ signaling plays a crucial role in conferring cold tolerance in plants. However, the role of Ca2+ involved in cold stress response needs to be further elucidated. Recent studies have shown how the perception of cold signals regulate Ca2+ channels to induce Ca2+ transients. In addition, studies have shown how Ca2+ signaling and its cross-talk with nitric oxide (NO), reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) signaling pathways ultimately lead to establishing cold tolerance in plants. Ca2+ signaling also plays a key role through Ca2+/calmodulin-mediated Arabidopsis signal responsive 1 (AtSR1/CAMTA3) when temperatures drop rapidly. This review highlights the current status in Ca2+ signaling-mediated cold tolerance in plants.
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2.
Fine-tuning of store-operated calcium entry by fast and slow Ca2+-dependent inactivation: Involvement of SARAF.
Jardín, I, Albarran, L, Salido, GM, López, JJ, Sage, SO, Rosado, JA
Biochimica et biophysica acta. Molecular cell research. 2018;(3):463-469
Abstract
Store-operated Ca2+ entry (SOCE) is a functionally relevant mechanism for Ca2+ influx present in electrically excitable and non-excitable cells. Regulation of Ca2+ entry through store-operated channels is essential to maintain an appropriate intracellular Ca2+ homeostasis and prevent cell damage. Calcium-release activated channels exhibit Ca2+-dependent inactivation mediated by two temporally separated mechanisms: fast Ca2+-dependent inactivation takes effect in the order of milliseconds and involves the interaction of Ca2+ with residues in the channel pore while slow Ca2+-dependent inactivation (SCDI) develops over tens of seconds, requires a global rise in [Ca2+]cyt and is a mechanism regulated by mitochondria. Recent studies have provided evidence that the protein SARAF (SOCE-associated regulatory factor) is involved in the mechanism underlying SCDI of Orai1. SARAF is an endoplasmic reticulum (ER) membrane protein that associates with STIM1 and translocate to plasma membrane-ER junctions in a STIM1-dependent manner upon store depletion to modulate SOCE. SCDI mediated by SARAF depends on the location of the STIM1-Orai1 complex within a PI(4,5)P2-rich microdomain. SARAF also interacts with Orai1 and TRPC1 in cells endogenously expressing STIM1 and cells with a low STIM1 expression and modulates channel function. This review focuses on the modulation by SARAF of SOCE and other forms of Ca2+ influx mediated by Orai1 and TRPC1 in order to provide spatio-temporally regulated Ca2+ signals.
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3.
MiR-128-3p directly targets VEGFC/VEGFR3 to modulate the proliferation of lymphatic endothelial cells through Ca2+ signaling.
Zhou, J, He, Z, Guo, L, Zeng, J, Liang, P, Ren, L, Zhang, M, Zhang, P, Huang, X
The international journal of biochemistry & cell biology. 2018;:51-58
Abstract
Lymphangiogenesis has been regarded as a physiological response to pathologic stimuli. The abnormal proliferation of lymphatic endothelial cell (LECs) and lymphangiogenesis is involved in the development of lymphatic disorders. Reportedly, VEGFC/VEGFR3 plays a key role in lymphangiogenesis; moreover, VEGFC/VEGFR3 exerts their cellular effects through activation of Ca2+ signaling in several cell types. Herein, we demonstrated that VEGFC significantly up-regulated LEC proliferation through VEGFR3; moreover, VEGFC/VEGFR3 induced Ca2+ signaling activation. By using online tools, miR-128 and miR-3916 were predicted as candidate upstream miRNAs which might target VEGFC/VEGFR3. As verified using Immunoblotting assays, miR-128 significantly regulated the protein levels of VEGFC/VEGFR3, whereas miR-3916 only slightly modulated VEGFC and VEGFR3 proteins. Contrary to VEGFC, miR-128 overexpression remarkably suppressed LEC proliferation, Ca2+ release and ERK1/2-Akt signaling; moreover, the effect of VEGFC could be partially attenuated by miR-128. In summary, miR-128 interacts with the 3'-UTR of VEGFC and VEGFR3 to inhibit their expression, thus suppressing LEC proliferation through Ca2+ and ERK1/2-Akt signaling. Taken together, we provided novel experimental basis for miRNA-regulated LEC proliferation through Ca2+ signaling.
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4.
Calcium-Activated Cl- Channel: Insights on the Molecular Identity in Epithelial Tissues.
Rottgen, TS, Nickerson, AJ, Rajendran, VM
International journal of molecular sciences. 2018;(5)
Abstract
Calcium-activated chloride secretion in epithelial tissues has been described for many years. However, the molecular identity of the channel responsible for the Ca2+-activated Cl− secretion in epithelial tissues has remained a mystery. More recently, TMEM16A has been identified as a new putative Ca2+-activated Cl− channel (CaCC). The primary goal of this article will be to review the characterization of TMEM16A, as it relates to the physical structure of the channel, as well as important residues that confer voltage and Ca2+-sensitivity of the channel. This review will also discuss the role of TMEM16A in epithelial physiology and potential associated-pathophysiology. This will include discussion of developed knockout models that have provided much needed insight on the functional localization of TMEM16A in several epithelial tissues. Finally, this review will examine the implications of the identification of TMEM16A as it pertains to potential novel therapies in several pathologies.
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5.
Projection length stimulated by oxytocin is modulated by the inhibition of calcium signaling in U-87MG cells.
Zatkova, M, Bacova, Z, Puerta, F, Lestanova, Z, Alanazi, M, Kiss, A, Reichova, A, Castejon, AM, Ostatnikova, D, Bakos, J
Journal of neural transmission (Vienna, Austria : 1996). 2018;(12):1847-1856
Abstract
Neuropeptide oxytocin contributes to the regulation of glial cell morphology. The precise mechanisms, however, are not yet fully understood. In the present study, we have investigated whether an oxytocin-induced increase of intracellular calcium is required for cell extension in astrocyte-like U-87MG cells. Oxytocin (1 µM) significantly increased the length of the cell projections measured by the green-fluorescent protein labeled microtubule-associated protein after 48 h. The knockdown of oxytocin receptors (OXTR) in U-87MG cells prevented the elongation of the projections. Incubation of U-87MG cells in the presence of oxytocin, resulted in a significant increase of intracellular calcium, specifically blocked by the OXTR antagonist L-371,257. Both quercetin, which is a phosphoinositide 3-kinase inhibitor, and the phospholipase C inhibitor U-73122 reduced oxytocin-induced elevation of intracellular calcium concentration. Conversely, neither diltiazem, an L-type voltage-gated calcium channel blocker nor tetracaine, which is a blocker of the ryanodine receptors, showed an effect on intracellular calcium levels. Treatment of cells with quercetin, U-73122 and the voltage-gated calcium channel blockers cilnidipine, ω-agatoxin and mibefradil prevented the elongation of projections stimulated by oxytocin. Oxytocin treatment resulted in a significant increase in gene and protein expression of the scaffolding protein SHANK3. Our results clearly show that activation of OXTRs contributes to the elongation of cell projections in astrocyte-like U-87MG cells and that this effect is mediated by an extracellular calcium influx accompanied by an increase in scaffolding proteins expression.
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6.
Human T cells in silico: Modelling dynamic intracellular calcium and its influence on cellular electrophysiology.
Eichinger, P, Herrmann, AM, Ruck, T, Herty, M, Gola, L, Kovac, S, Budde, T, Meuth, SG, Hundehege, P
Journal of immunological methods. 2018;:78-84
Abstract
A network of ion currents influences basic cellular T cell functions. After T cell receptor activation, changes in highly regulated calcium levels play a central role in triggering effector functions and cell differentiation. A dysregulation of these processes might be involved in the pathogenesis of several diseases. We present a mathematical model based on the NEURON simulation environment that computes dynamic calcium levels in combination with the current output of diverse ion channels (KV1.3, KCa3.1, K2P channels (TASK1-3, TRESK), VRAC, TRPM7, CRAC). In line with experimental data, the simulation shows a strong increase in intracellular calcium after T cell receptor stimulation before reaching a new, elevated calcium plateau in the T cell's activated state. Deactivation of single ion channel modules, mimicking the application of channel blockers, reveals that two types of potassium channels are the main regulators of intracellular calcium level: calcium-dependent potassium (KCa3.1) and two-pore-domain potassium (K2P) channels.
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7.
Cross talk between β subunits, intracellular Ca2+ signaling, and SNAREs in the modulation of CaV 2.1 channel steady-state inactivation.
Serra, SA, Gené, GG, Elorza-Vidal, X, Fernández-Fernández, JM
Physiological reports. 2018;(2)
Abstract
Modulation of CaV 2.1 channel activity plays a key role in interneuronal communication and synaptic plasticity. SNAREs interact with a specific synprint site at the second intracellular loop (LII-III) of the CaV 2.1 pore-forming α1A subunit to optimize neurotransmitter release from presynaptic terminals by allowing secretory vesicles docking near the Ca2+ entry pathway, and by modulating the voltage dependence of channel steady-state inactivation. Ca2+ influx through CaV 2.1 also promotes channel inactivation. This process seems to involve Ca2+ -calmodulin interaction with two adjacent sites in the α1A carboxyl tail (C-tail) (the IQ-like motif and the Calmodulin-Binding Domain (CBD) site), and contributes to long-term potentiation and spatial learning and memory. Besides, binding of regulatory β subunits to the α interaction domain (AID) at the first intracellular loop (LI-II) of α1A determines the degree of channel inactivation by both voltage and Ca2+ . Here, we explore the cross talk between β subunits, Ca2+ , and syntaxin-1A-modulated CaV 2.1 inactivation, highlighting the α1A domains involved in such process. β3 -containing CaV 2.1 channels show syntaxin-1A-modulated but no Ca2+ -dependent steady-state inactivation. Conversely, β2a -containing CaV 2.1 channels show Ca2+ -dependent but not syntaxin-1A-modulated steady-state inactivation. A LI-II deletion confers Ca2+ -dependent inactivation and prevents modulation by syntaxin-1A in β3 -containing CaV 2.1 channels. Mutation of the IQ-like motif, unlike CBD deletion, abolishes Ca2+ -dependent inactivation and confers modulation by syntaxin-1A in β2a -containing CaV 2.1 channels. Altogether, these results suggest that LI-II structural modifications determine the regulation of CaV 2.1 steady-state inactivation either by Ca2+ or by SNAREs but not by both.
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8.
Neutrophil activation in response to monomeric myeloperoxidase.
Gorudko, IV, Grigorieva, DV, Sokolov, AV, Shamova, EV, Kostevich, VA, Kudryavtsev, IV, Syromiatnikova, ED, Vasilyev, VB, Cherenkevich, SN, Panasenko, OM
Biochemistry and cell biology = Biochimie et biologie cellulaire. 2018;(5):592-601
Abstract
Myeloperoxidase (MPO) is an oxidant-producing enzyme that can also regulate cellular functions via its nonenzymatic effects. Mature active MPO isolated from normal human neutrophils is a 145 kDa homodimer, which consists of 2 identical protomers, connected by a single disulfide bond. By binding to CD11b/CD18 integrin, dimeric MPO induces neutrophil activation and adhesion augmenting leukocyte accumulation at sites of inflammation. This study was performed to compare the potency of dimeric and monomeric MPO to elicit selected neutrophil responses. Monomeric MPO (hemi-MPO) was obtained by treating the dimeric MPO by reductive alkylation. Analysis of the crucial signal transducer, intracellular Ca2+, showed that dimeric MPO induces Ca2+ mobilization from the intracellular calcium stores of neutrophils and influx of extracellular Ca2+ whereas the effect of monomeric MPO on Ca2+ increase in neutrophils was less. It was also shown that monomeric MPO was less efficient than dimeric MPO at inducing actin cytoskeleton reorganization, cell survival, and neutrophil degranulation. Furthermore, we have detected monomeric MPO in the blood plasma of patients with acute inflammation. Our data suggest that the decomposition of dimeric MPO into monomers can serve as a regulatory mechanism that controls MPO-dependent activation of neutrophils and reduces the proinflammatory effects of MPO.
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9.
Manipulating Intracellular Ca2+ Signals to Stimulate Therapeutic Angiogenesis in Cardiovascular Disorders.
Moccia, F, Berra-Romani, R, Rosti, V
Current pharmaceutical biotechnology. 2018;(9):686-699
Abstract
Endothelial progenitor cells (EPCs) are mobilized in peripheral blood to rescue blood perfusion in ischemic tissues. Several approaches were, therefore, designed to inject autologous EPCs and induce therapeutic angiogenesis in patients affected by cardiovascular disorders. Endothelial colony forming cells (ECFCs) represent the only truly endothelial precursors and are regarded as the most suitable substrate for cell based therapy of ischemic diseases. Intracellular Ca2+ signalling drives ECFC proliferation, migration, homing and neovessel formation. Vascular endothelial growth factor (VEGF) triggers repetitive oscillations in intracellular Ca2+ concentration ([Ca2+]i) in peripheral blood- and umbilical cord blood-derived ECFCs by initiating a dynamic interplay between inositol-1,4,5-trisphosphate (InsP3)-dependent Ca2+ release and store-operated Ca2+ entry (SOCE). SOCE, in turn, is mediated by Stim1, Orai1 and Transient Receptor Potential (TRP) Canonical 1 (TRPC1). Intriguingly, intracellular Ca2+ oscillations are triggered by TRPC3 in umbilical cord blood-derived ECFCs, which display higher proliferative potential. Additionally, stromal cell-derived factor-1α (SDF-1α) triggers a biphasic increase in [Ca2+]i in ECFCs which is mediated by InsP3 receptors (InsP3Rs) and SOCE. Finally, arachidonic acid (AA) and nicotinic acid adenine dinucleotide phosphate (NAADP) stimulate ECFC proliferation by stimulating two-pore channel 1 (TPC1), thereby promoting Ca2+ release from the endolysosomal Ca2+ compartment. AA-evoked Ca2+ signals are further supported by InsP3Rs and TRP Vanilloid 4 (TRPV4). In this article, we describe how genetic manipulation of the Ca2+ toolkit (i.e. TRPC3, SOCE, TPC1) endowed to circulating ECFCs could rejuvenate or restore their reparative phenotype for therapeutic angiogenesis purposes.
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10.
Calcium Dynamics as a Machine for Decoding Signals.
Giorgi, C, Danese, A, Missiroli, S, Patergnani, S, Pinton, P
Trends in cell biology. 2018;(4):258-273
Abstract
Calcium (Ca2+) is considered one of the most-important biological cations, because it is implicated in cell physiopathology and cell fate through a finely tuned signaling system. In support of this notion, Ca2+ is the primary driver of cell proliferation and cell growth; however, it is also intimately linked to cell death. Functional abnormalities or mutations in proteins that mediate Ca2+ homeostasis usually lead to a plethora of diseases and pathogenic states, including cancer, heart failure, diabetes, and neurodegenerative disease. In this review, we examine recent discoveries in the highly localized nature of Ca2+-dependent signal transduction and its roles in cell fate, inflammasome activation, and synaptic transmission.