Shaping the calcium signature McAinsh, Martin R.; Pittman, Jon K.
The New phytologist,
January 2009, Letnik:
181, Številka:
2
Journal Article
Recenzirano
Summary 275 I. Introduction 276 II. Ca²⁺ signalling pathways 276 III. Shaping Ca²⁺ signatures 278 IV. Ca²⁺ influx channels 278 V. Ca²⁺ influx channels as modulators of Ca²⁺ signatures 281 VI. Ca²⁺ ...efflux transporters 282 VII. Ca²⁺ efflux transporters as modulators of Ca²⁺ signatures 284 VIII. The shaping of noncytosolic Ca²⁺ signatures 285 IX. Future insights into the role of Ca²⁺ oscillators from modelling studies 287 X. Conclusions and perspectives 288 Acknowledgements 288 References 288 In numerous plant signal transduction pathways, Ca²⁺ is a versatile second messenger which controls the activation of many downstream actions in response to various stimuli. There is strong evidence to indicate that information encoded within these stimulus-induced Ca²⁺ oscillations can provide signalling specificity. Such Ca²⁺ signals, or 'Ca²⁺ signatures', are generated in the cytosol, and in noncytosolic locations including the nucleus and chloroplast, through the coordinated action of Ca²⁺ influx and efflux pathways. An increased understanding of the functions and regulation of these various Ca²⁺ transporters has improved our appreciation of the role these transporters play in specifically shaping the Ca²⁺ signatures. Here we review the evidence which indicates that Ca²⁺ channel, Ca²⁺-ATPase and Ca²⁺ exchanger isoforms can indeed modulate specific Ca²⁺ signatures in response to an individual signal.
Cellular Ca2+ signaling functions as one of the most common second messengers of various signal transduction pathways in cells and mediates a number of physiological roles in a cell-type dependent ...manner. Ca2+ signaling also regulates more general and fundamental cellular activities, including cell proliferation and apoptosis. Among ion channels, Ca2+-permeable channels in the plasma membrane as well as endo- and sarcoplasmic reticulum membranes play important roles in Ca2+ signaling by directly contributing to the influx of Ca2+ from extracellular spaces or its release from storage sites, respectively. Furthermore, Ca2+-gated ion channels in the plasma membrane often crosstalk reciprocally with Ca2+ signals and are central to the regulation of cellular functions. This review focuses on the physiological and pharmacological impact of i) Ca2+-gated ion channels as an apparatus for the conversion of cellular Ca2+ signals to intercellularly propagative electrical signals and ii) the opposite feedback regulation of Ca2+ signaling by Ca2+-gated ion channel activities in excitable and non-excitable cells.
Intracellular Ca2+ signaling is witnessing an amazing resurgence of interest. In addition to traditional Ca2+ aficionados, an astonishing (and growing) number of colleagues from all around the world ...have started to devote a large part of their research to gain insights into the role of Ca2+ signaling in health and disease. This is why calcium ions interact with virtually every signal transduction pathway not only in mammalian cells, but also across the phylogenetic tree, thereby, driving or modulating most, if not all, cellular functions, ranging from fertilization to apoptosis, passing through learning and memory, cardiac contractility, and immune response. This book gathers a collection of original research articles and reviews by a number of renowned experts who aim to present the state of the art of many pathophysiological aspects of intracellular Ca2+ signaling, such as embryonic development, immune response, extracellular Ca2+ signaling, neoplastic transformation, muscle hypertrophy, pulmonary inflammation, and P2X receptor gating.
We developed a method to evaluate the activity of the Na+–Ca2+ exchanger (NCX) and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) with fluorescence microscopy in mouse ventricular cardiomyocytes. In ...non-beating ventricular cardiomyocytes, α-adrenoceptor stimulation by phenylephrine caused a decrease in the cytoplasmic Ca2+ concentration, which was inhibited by SEA0400, an NCX inhibitor, but not cyclopiazonic acid, a SERCA inhibitor. β-Adrenoceptor stimulation by isoprenaline caused a decrease in the cytoplasmic Ca2+ concentration, which was inhibited by cyclopiazonic acid but not SEA0400. Ellagic acid, a phenolic phytochemical, also decreased the basal Ca2+ concentration, which was inhibited by cyclopiazonic acid, but not SEA0400. Thus, this method using fluorescent microscopy and specific inhibitors would be useful for the evaluation of pharmacological agents acting on NCX and SERCA.
At any moment in time, cells coordinate and balance their calcium ion (Ca
2+
) fluxes. The term ‘Ca
2+
homeostasis’ suggests that balancing resting Ca
2+
levels is a rather static process. However, ...direct ER Ca
2+
imaging shows that resting Ca
2+
levels are maintained by surprisingly dynamic Ca
2+
fluxes between the ER Ca
2+
store, the cytosol, and the extracellular space. The data show that the ER Ca
2+
leak, continuously fed by the high-energy consuming SERCA, is a fundamental driver of resting Ca
2+
dynamics. Based on simplistic Ca
2+
toolkit models, we discuss how the ER Ca
2+
leak could contribute to evolutionarily conserved Ca
2+
phenomena such as Ca
2+
entry, ER Ca
2+
release, and Ca
2+
oscillations.
The effect of KB-R7943, an inhibitor of the plasmalemmal Na+ -Ca2+ exchanger, on mitochondrial Ca2+ transporters was examined with membrane-permeabilized cardiomyocyte-derived H9c2 cells expressing ...the fluorescent Ca2+ indicator, yellow cameleon 3.1, in the mitochondria. KB-R7943, as well as ruthenium red, inhibited the rise in mitochondrial Ca2+ on increasing the extramitochondrial Ca2+ concentration from 0 nM to 300nM. CGP-37157, but not KB-R7943, inhibited the decline in mitochondrial Ca2+ on return to Ca2+ free extramitochondrial solution. These results indicated that KB-R7943 has inhibitory effects on the mitochondrial Ca2+ uniporter, but not on the mitochondrial Na+ -Ca2+ exchanger.
The WFS1 gene, encoding an endoplasmic reticulum (ER) membrane glycoprotein, is mutated in Wolfram syndrome characterized by diabetes mellitus and optic atrophy. Herein, Ca2+ dynamics were examined ...in WFS1‐knockdown and ‐overexpressing HEK293 cells. Studies using ER‐targeted Ca2+‐sensitive photoprotein aequorin demonstrated WFS1 protein to positively modulate ER Ca2+ levels by increasing the rate of Ca2+ uptake. Furthermore, Ca2+ imaging with Fura‐2 showed the magnitude of the store‐operated Ca2+ entry to parallel WFS1 expression levels. These data indicate that WFS1 protein participates in the regulation of cellular Ca2+ homeostasis, at least partly, by modulating the filling state of the ER Ca2+ store.
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•Calcium (Ca2+) signaling is dysregulated in aging neurons and in neurons affected by neurodegenerative disorders.•Elevated endoplasmic reticulum (ER) Ca2+ levels and reduced neuronal ...store-operated Ca2+ entry (SOCE) are linked with synaptic loss in Alzheimer’s disease.•Reduced ER Ca2+ levels and enhanced SOCE are linked with synaptic loss in Huntington’s disease.•Reduced SOCE and reduced ER Ca2+ levels are linked with neuronal cell death in Parkinson’s disease.
Calcium (Ca2+) is a ubiquitous second messenger that regulates various activities in eukaryotic cells. Especially important role calcium plays in excitable cells. Neurons require extremely precise spatial-temporal control of calcium-dependent processes because they regulate such vital functions as synaptic plasticity. Recent evidence indicates that neuronal calcium signaling is abnormal in many of neurodegenerative disorders such as Alzheimer’s disease (AD), Huntington’s disease (HD) and Parkinson’s disease (PD). These diseases represent a major medical, social, financial and scientific problem, but despite enormous research efforts, they are still incurable and only symptomatic relief drugs are available. Thus, new approaches and targets are needed. This review highlight neuronal calcium-signaling abnormalities in these diseases, with particular emphasis on the role of neuronal store-operated Ca2+ entry (SOCE) pathway and its potential relevance as a therapeutic target for treatment of neurodegeneration.
Varying pH of luminal fluid along the female reproductive tract is a physiological cue that modulates sperm motility. CatSper is a sperm-specific, pH-sensitive calcium channel essential for ...hyperactivated motility and male fertility. Multi-subunit CatSper channel complexes organize linear Ca2+ signaling nanodomains along the sperm tail. Here, we identify EF-hand calcium-binding domain-containing protein 9 (EFCAB9) as a bifunctional, cytoplasmic machine modulating the channel activity and the domain organization of CatSper. Knockout mice studies demonstrate that EFCAB9, in complex with the CatSper subunit, CATSPERζ, is essential for pH-dependent and Ca2+-sensitive activation of the CatSper channel. In the absence of EFCAB9, sperm motility and fertility is compromised, and the linear arrangement of the Ca2+ signaling domains is disrupted. EFCAB9 interacts directly with CATSPERζ in a Ca2+-dependent manner and dissociates at elevated pH. These observations suggest that EFCAB9 is a long-sought, intracellular, pH-dependent Ca2+ sensor that triggers changes in sperm motility.
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•Efcab9 encodes an evolutionarily conserved, sperm-specific EF-hand domain protein•Efcab9-deficient mice have sperm motility defects and compromised male fertility•EFCAB9 senses both pH and Ca2+ helping regulate flagellar CatSper channel activity
A pH-dependent calcium sensor enables modulation of sperm motility in response to changing conditions along the female reproductive tract.
Oxytocin (OXT) receptors (OXTRs) are prominently expressed in hippocampal CA2 and CA3 pyramidal neurons, but little is known about its physiological function. As the functional necessity of ...hippocampal CA2 for social memory processing, we tested whether CA2 OXTRs may contribute to long-term social recognition memory (SRM) formation. Here, we found that conditional deletion of
from forebrain (
) or CA2/CA3a-restricted excitatory neurons in adult male mice impaired the persistence of long-term SRM but had no effect on sociability and preference for social novelty. Conditional deletion of CA2/CA3a
showed no changes in anxiety-like behavior assessed using the open-field, elevated plus maze and novelty-suppressed feeding tests. Application of a highly selective OXTR agonist Thr
,Gly
-OXT to hippocampal slices resulted in an acute and lasting potentiation of excitatory synaptic responses in CA2 pyramidal neurons that relied on
-methyl-d-aspartate receptor activation and calcium/calmodulin-dependent protein kinase II activity. In addition,
mice displayed a defect in the induction of long-term potentiation, but not long-term depression, at the synapses between the entorhinal cortex and CA2 pyramidal neurons. Furthermore,
deletion led to a reduced complexity of basal dendritic arbors of CA2 pyramidal neurons, but caused no alteration in the density of apical dendritic spines. Considering that the methodologies we have used to delete
do not rule out targeting the neighboring CA3a region, these findings suggest that OXTR signaling in the CA2/CA3a is crucial for the persistence of long-term SRM.
Oxytocin receptors (OXTRs) are abundantly expressed in hippocampal CA2 and CA3 regions, but there are little known about their physiological function. Taking advantage of the conditional
knock-out mice, the present study highlights the importance of OXTR signaling in the induction of long-term potentiation at the synapses between the entorhinal cortex and CA2 pyramidal neurons and the persistence of long-term social recognition memory. Thus, OXTRs in the CA2/CA3a may provide a new target for therapeutic approaches to the treatment of social cognition deficits, which are often observed in patients with neuropsychiatric disorders.
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