Ca 2+ : a versatile master key for intracellular signaling cascades (original) (raw)
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The ins and outs of cellular Ca2+ transport
Current Opinion in Plant Biology, 2011
The cytoplasmic Ca 2+ signals that participate in nearly all aspects of plant growth and development encode information as binary switches or information-rich signatures. They are the result of influx (thermodynamically passive) and efflux (thermodynamically active) activities mediated by membrane transport proteins. On the influx side, confirming the molecular identities of Ca 2+-permeable channels is still a major research topic. Cyclic nucleotide-gated channels and glutamate receptor-like channels are candidates well supported by evidence. On the efflux side, CAX antiporters and P-type ATPase pumps are the principal molecular entities. Both of these active transporters load Ca 2+ into specific compartments and have the potential to reduce the magnitude and duration of a Ca 2+ transient. Recent studies indicate calmodulin-activated Ca 2+ pumps in endomembrane systems can dampen the magnitude and duration of a Ca 2+ transient that could otherwise grow into a Ca 2+ cell-death signature. An important challenge following molecular characterization of the influx and efflux pathways is to understand how they are coordinately regulated to produce a Ca 2+ switch or encode specific information into a Ca 2+ signature.
Calcium and cancer: targeting Ca2+ transport
Nature Reviews …, 2007
The calcium ion (Ca 2+ ) regulates various cellular processes by activating or inhibiting cellular signalling pathways and Ca 2+ -regulated proteins. These processes range from muscle contraction to synaptic transmission, and from cellular proliferation to apoptosis 1 . Some Ca 2+ -mediated signalling pathways are implicated in tumorigenesis and tumour progression, such as metastasis, invasion and angio genesis. These and other cancer-relevant Ca 2+ -regulated pathways are summarized in BOX 1.
Calcium signalling: Past, present and future
Cell Calcium, 2005
Ca 2+ is a universal second messenger controlling a wide variety of cellular reactions and adaptive responses. The initial appreciation of Ca 2+ as a universal signalling molecule was based on the work of Sydney Ringer and Lewis Heilbrunn. More recent developments in this field were critically influenced by the invention of the patch clamp technique and the generation of fluorescent Ca 2+ indicators. Currently the molecular Ca 2+ signalling mechanisms are being worked out and we are beginning to assemble a reasonably complete picture of overall Ca 2+ homeostasis. Furthermore, investigations of organellar Ca 2+ homeostasis have added complexity to our understanding of Ca 2+ signalling. The future of the Ca 2+ signalling field lies with detailed investigations of the integrative function in vivo and clarification of the pathology associated with malfunctions of Ca 2+ signalling cascades.
Cold Spring Harbor perspectives in biology, 2011
Calcium is an ambivalent signal: it is essential for the correct functioning of cell life, but may also become dangerous to it. The plasma membrane Ca(2+) ATPase (PMCA) and the plasma membrane Na(+)/Ca(2+) exchanger (NCX) are the two mechanisms responsible for Ca(2+) extrusion. The NCX has low Ca(2+) affinity but high capacity for Ca(2+) transport, whereas the PMCA has a high Ca(2+) affinity but low transport capacity for it. Thus, traditionally, the PMCA pump has been attributed a housekeeping role in maintaining cytosolic Ca(2+), and the NCX the dynamic role of counteracting large cytosolic Ca(2+) variations (especially in excitable cells). This view of the roles of the two Ca(2+) extrusion systems has been recently revised, as the specific functional properties of the numerous PMCA isoforms and splicing variants suggests that they may have evolved to cover both the basal Ca(2+) regulation (in the 100 nM range) and the Ca(2+) transients generated by cell stimulation (in the μM ran...
Calcium Signalling and Regulation of Cell Function
eLS, 2001
The calcium ion (Ca 2+ ) is a versatile intracellular messenger. It provides dynamic regulation of vast array of cellular processes such as gene transcription, differentiation and contraction. Ca 2+ signals range from microsecond, nanoscopic events to intercellular waves lasting for many seconds. This diversity of Ca 2+ signals arises from the wide assortment of Ca 2+ transport and Ca 2+ buffering processes employed by cells. Additional diversity in Ca 2+ signalling stems from the ability of cells to utilise different sources of Ca 2+ . The cytosol is the principal Ca 2+ signalling compartment. When Ca 2+ ions enter the cytosol they interact with numerous Ca 2+ -binding proteins, thereby leading to activation, or inhibition, of cellular processes. Specificity is achieved by regulating the spatial and kinetic properties of Ca 2+ signal. In this way, many concurrent Ca 2+ -sensitive cellular processes can be discretely regulated. A number of pathologies have been related to the breakdown of cellular Ca 2+ homoeostasis or to aberrant Ca 2+ signalling.
Calcium and ATP control multiple vital functions
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2016
Life on Planet Earth, as we know it, revolves around adenosine triphosphate (ATP) as a universal energy storing molecule. The metabolism of ATP requires a low cytosolic Ca(2+) concentration, and hence tethers these two molecules together. The exceedingly low cytosolic Ca(2+) concentration (which in all life forms is kept around 50-100 nM) forms the basis for a universal intracellular signalling system in which Ca(2+) acts as a second messenger. Maintenance of transmembrane Ca(2+) gradients, in turn, requires ATP-dependent Ca(2+) transport, thus further emphasizing the inseparable links between these two substances. Ca(2+) signalling controls the most fundamental processes in the living organism, from heartbeat and neurotransmission to cell energetics and secretion. The versatility and plasticity of Ca(2+) signalling relies on cell specific Ca(2+) signalling toolkits, remodelling of which underlies adaptive cellular responses. Alterations of these Ca(2+) signalling toolkits lead to a...
Intracellular Ca2+ signalling: unexpected new roles for the usual suspect
Frontiers in Physiology, 2023
Cytosolic Ca 2+ signals are organized in complex spatial and temporal patterns that underlie their unique ability to regulate multiple cellular functions. Changes in intracellular Ca 2+ concentration ([Ca 2+ ] i) are finely tuned by the concerted interaction of membrane receptors and ion channels that introduce Ca 2+ into the cytosol, Ca 2+-dependent sensors and effectors that translate the elevation in [Ca 2+ ] i into a biological output, and Ca 2+-clearing mechanisms that return the [Ca 2+ ] i to prestimulation levels and prevent cytotoxic Ca 2+ overload. The assortment of the Ca 2+ handling machinery varies among different cell types to generate intracellular Ca 2+ signals that are selectively tailored to subserve specific functions. The advent of novel high-speed, 2D and 3D time-lapse imaging techniques, single-wavelength and genetic Ca 2+ indicators, as well as the development of novel genetic engineering tools to manipulate single cells and whole animals, has shed novel light on the regulation of cellular activity by the Ca 2+ handling machinery. A symposium organized within the framework of the 72nd Annual Meeting of the Italian Society of Physiology, held in Bari on 14-16th September 2022, has recently addressed many of the unexpected mechanisms whereby intracellular Ca 2+ signalling regulates cellular fate in healthy and disease states. Herein, we present a report of this symposium, in which the following emerging topics were discussed: 1) Regulation of water reabsorption in the kidney by lysosomal Ca 2+ release through Transient Receptor Potential Mucolipin 1 (TRPML1); 2) Endoplasmic reticulum-to-mitochondria Ca 2+ transfer in Alzheimer's disease-related astroglial dysfunction; 3) The non-canonical role of TRP Melastatin 8 (TRPM8) as a Rap1A inhibitor in the definition of some cancer hallmarks; and 4) Non-genetic optical stimulation of Ca 2+ signals in the cardiovascular system.
Calcium signaling in physiology and pathophysiology
Acta Pharmacologica Sinica, 2006
Calcium ions are the most ubiquitous and pluripotent cellular signaling molecules that control a wide variety of cellular processes. The calcium signaling system is represented by a relatively limited number of highly conserved transporters and channels, which execute Ca 2+ movements across biological membranes and by many thousands of Ca 2+ -sensitive effectors. Molecular cascades, responsible for the generation of calcium signals, are tightly controlled by Ca 2+ ions themselves and by genetic factors, which tune the expression of different Ca 2+ -handling molecules according to adaptational requirements. Ca 2+ ions determine normal physiological reactions and the development of many pathological processes.