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Cells Aug 2021Calcium (Ca) functions as a second messenger that is critical in regulating fundamental physiological functions such as cell growth/development, cell survival, neuronal... (Review)
Review
Calcium (Ca) functions as a second messenger that is critical in regulating fundamental physiological functions such as cell growth/development, cell survival, neuronal development and/or the maintenance of cellular functions. The coordination among various proteins/pumps/Ca channels and Ca storage in various organelles is critical in maintaining cytosolic Ca levels that provide the spatial resolution needed for cellular homeostasis. An important regulatory aspect of Ca homeostasis is a store operated Ca entry (SOCE) mechanism that is activated by the depletion of Ca from internal ER stores and has gained much attention for influencing functions in both excitable and non-excitable cells. Ca has been shown to regulate opposing functions such as autophagy, that promote cell survival; on the other hand, Ca also regulates programmed cell death processes such as apoptosis. The functional significance of the TRP/Orai channels has been elaborately studied; however, information on how they can modulate opposing functions and modulate function in excitable and non-excitable cells is limited. Importantly, perturbations in SOCE have been implicated in a spectrum of pathological neurodegenerative conditions. The critical role of autophagy machinery in the pathogenesis of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases, would presumably unveil avenues for plausible therapeutic interventions for these diseases. We thus review the role of SOCE-regulated Ca signaling in modulating these diverse functions in stem cell, immune regulation and neuromodulation.
Topics: Animals; Autophagy; Calcium; Calcium Channels; Calcium Signaling; Humans; Stem Cells
PubMed: 34440894
DOI: 10.3390/cells10082125 -
Nature Neuroscience Feb 2016The discovery that transient elevations of calcium concentration occur in astrocytes, and release 'gliotransmitters' which act on neurons and vascular smooth muscle, led... (Review)
Review
The discovery that transient elevations of calcium concentration occur in astrocytes, and release 'gliotransmitters' which act on neurons and vascular smooth muscle, led to the idea that astrocytes are powerful regulators of neuronal spiking, synaptic plasticity and brain blood flow. These findings were challenged by a second wave of reports that astrocyte calcium transients did not mediate functions attributed to gliotransmitters and were too slow to generate blood flow increases. Remarkably, the tide has now turned again: the most important calcium transients occur in fine astrocyte processes not resolved in earlier studies, and new mechanisms have been discovered by which astrocyte [Ca(2+)]i is raised and exerts its effects. Here we review how this third wave of discoveries has changed our understanding of astrocyte calcium signaling and its consequences for neuronal function.
Topics: Animals; Astrocytes; Calcium Signaling; Humans; Neuroglia; Neurotransmitter Agents
PubMed: 26814587
DOI: 10.1038/nn.4201 -
Circulation Research Jul 2017Cardiac contractility is regulated by changes in intracellular Ca concentration ([Ca]). Normal function requires that [Ca] be sufficiently high in systole and low in... (Review)
Review
Cardiac contractility is regulated by changes in intracellular Ca concentration ([Ca]). Normal function requires that [Ca] be sufficiently high in systole and low in diastole. Much of the Ca needed for contraction comes from the sarcoplasmic reticulum and is released by the process of calcium-induced calcium release. The factors that regulate and fine-tune the initiation and termination of release are reviewed. The precise control of intracellular Ca cycling depends on the relationships between the various channels and pumps that are involved. We consider 2 aspects: (1) structural coupling: the transporters are organized within the dyad, linking the transverse tubule and sarcoplasmic reticulum and ensuring close proximity of Ca entry to sites of release. (2) Functional coupling: where the fluxes across all membranes must be balanced such that, in the steady state, Ca influx equals Ca efflux on every beat. The remainder of the review considers specific aspects of Ca signaling, including the role of Ca buffers, mitochondria, Ca leak, and regulation of diastolic [Ca].
Topics: Animals; Calcium; Calcium Signaling; Excitation Contraction Coupling; Humans; Intracellular Fluid; Mitochondria, Heart; Myocytes, Cardiac; Sarcoplasmic Reticulum
PubMed: 28684623
DOI: 10.1161/CIRCRESAHA.117.310230 -
Trends in Cell Biology Apr 2023Calcium ion (Ca) is a ubiquitous and versatile signaling molecule controlling a wide variety of cellular processes, such as proliferation, cell death, migration, and... (Review)
Review
Calcium ion (Ca) is a ubiquitous and versatile signaling molecule controlling a wide variety of cellular processes, such as proliferation, cell death, migration, and immune response, all fundamental processes essential for the establishment of cancer. In recent decades, the loss of Ca homeostasis has been considered an important driving force in the initiation and progression of malignant diseases. The primary intracellular Ca store, the endoplasmic reticulum (ER), plays an essential role in maintaining Ca homeostasis by coordinating with other organelles and the plasma membrane. Here, we discuss the dysregulation of ER-centered Ca homeostasis in cancer, summarize Ca-based anticancer therapeutics, and highlight the significance of furthering our understanding of Ca homeostasis regulation in cancer.
Topics: Humans; Calcium; Endoplasmic Reticulum; Cell Death; Calcium Signaling; Neoplasms; Homeostasis
PubMed: 35915027
DOI: 10.1016/j.tcb.2022.07.004 -
Physiological Reviews Oct 2023Calcium signaling underlies much of physiology. Almost all the Ca in the cytoplasm is bound to buffers, with typically only ∼1% being freely ionized at resting levels... (Review)
Review
Calcium signaling underlies much of physiology. Almost all the Ca in the cytoplasm is bound to buffers, with typically only ∼1% being freely ionized at resting levels in most cells. Physiological Ca buffers include small molecules and proteins, and experimentally Ca indicators will also buffer calcium. The chemistry of interactions between Ca and buffers determines the extent and speed of Ca binding. The physiological effects of Ca buffers are determined by the kinetics with which they bind Ca and their mobility within the cell. The degree of buffering depends on factors such as the affinity for Ca, the Ca concentration, and whether Ca ions bind cooperatively. Buffering affects both the amplitude and time course of cytoplasmic Ca signals as well as changes of Ca concentration in organelles. It can also facilitate Ca diffusion inside the cell. Ca buffering affects synaptic transmission, muscle contraction, Ca transport across epithelia, and the killing of bacteria. Saturation of buffers leads to synaptic facilitation and tetanic contraction in skeletal muscle and may play a role in inotropy in the heart. This review focuses on the link between buffer chemistry and function and how Ca buffering affects normal physiology and the consequences of changes in disease. As well as summarizing what is known, we point out the many areas where further work is required.
Topics: Humans; Calcium; Buffers; Cytoplasm; Heart; Synaptic Transmission; Calcium Signaling
PubMed: 37326298
DOI: 10.1152/physrev.00042.2022 -
International Journal of Molecular... Nov 2020Calcium (Ca) is a major second messenger in cells and is essential for the fate and survival of all higher organisms. Different Ca channels, pumps, or exchangers... (Review)
Review
Calcium (Ca) is a major second messenger in cells and is essential for the fate and survival of all higher organisms. Different Ca channels, pumps, or exchangers regulate variations in the duration and levels of intracellular Ca, which may be transient or sustained. These changes are then decoded by an elaborate toolkit of Ca-sensors, which translate Ca signal to intracellular operational cell machinery, thereby regulating numerous Ca-dependent physiological processes. Alterations to Ca homoeostasis and signaling are often deleterious and are associated with certain pathological states, including cancer. Altered Ca transmission has been implicated in a variety of processes fundamental for the uncontrolled proliferation and invasiveness of tumor cells and other processes important for cancer progression, such as the development of resistance to cancer therapies. Here, we review what is known about Ca signaling and how this fundamental second messenger regulates life and death decisions in the context of cancer, with particular attention directed to cell proliferation, apoptosis, and autophagy. We also explore the intersections of Ca and the therapeutic targeting of cancer cells, summarizing the therapeutic opportunities for Ca signal modulators to improve the effectiveness of current anticancer therapies.
Topics: Animals; Apoptosis; Autophagy; Calcium; Calcium Channels; Calcium Signaling; Cell Proliferation; Homeostasis; Humans; Neoplasms; Signal Transduction
PubMed: 33171939
DOI: 10.3390/ijms21218323 -
Frontiers in Immunology 2023
Topics: Humans; Calcium Signaling; Neoplasms; Myeloid Cells
PubMed: 38022525
DOI: 10.3389/fimmu.2023.1315490 -
Cold Spring Harbor Perspectives in... Jul 2012Calcium ions control diverse cellular processes (e.g., muscle contraction, exocytosis, and motility). Cells use a “toolkit” of channels, pumps, and cytosolic buffers...
Calcium ions control diverse cellular processes (e.g., muscle contraction, exocytosis, and motility). Cells use a “toolkit” of channels, pumps, and cytosolic buffers to regulate calcium levels.
Topics: Animals; Calcium Signaling; Humans
PubMed: 22751152
DOI: 10.1101/cshperspect.a011171 -
Development (Cambridge, England) Sep 2022Calcium influx can be stimulated by various intra- and extracellular signals to set coordinated gene expression programs into motion. As such, the precise regulation of... (Review)
Review
Calcium influx can be stimulated by various intra- and extracellular signals to set coordinated gene expression programs into motion. As such, the precise regulation of intracellular calcium represents a nexus between environmental cues and intrinsic genetic programs. Mounting genetic evidence points to a role for the deregulation of intracellular calcium signaling in neuropsychiatric disorders of developmental origin. These findings have prompted renewed enthusiasm for understanding the roles of calcium during normal and dysfunctional prenatal development. In this Review, we describe the fundamental mechanisms through which calcium is spatiotemporally regulated and directs early neurodevelopmental events. We also discuss unanswered questions about intracellular calcium regulation during the emergence of neurodevelopmental disease, and provide evidence that disruption of cell-specific calcium homeostasis and/or redeployment of developmental calcium signaling mechanisms may contribute to adult neurological disorders. We propose that understanding the normal developmental events that build the nervous system will rely on gaining insights into cell type-specific calcium signaling mechanisms. Such an understanding will enable therapeutic strategies targeting calcium-dependent mechanisms to mitigate disease.
Topics: Calcium; Calcium Signaling; Cerebral Cortex; Humans; Nervous System Diseases
PubMed: 36102617
DOI: 10.1242/dev.198853 -
The FEBS Journal Nov 2021The old Greek aphorism 'Panta Rhei' ('everything flows') is true for all living things in general. As a dynamic process, calcium signaling plays fundamental roles in... (Review)
Review
The old Greek aphorism 'Panta Rhei' ('everything flows') is true for all living things in general. As a dynamic process, calcium signaling plays fundamental roles in cellular activities under both normal and pathological conditions, with recent researches uncovering its involvement in cell proliferation, migration, survival, gene expression, and more. The major question we address here is how calcium signaling affects cancer progression and whether it could be targeted to combine with classic chemotherapeutics or emerging immunotherapies to improve their efficacy.
Topics: Animals; Calcium Signaling; Humans; Neoplasms
PubMed: 34288422
DOI: 10.1111/febs.16133