Calcium signalling—an overview

Nature reviews. Molecular cell biology, 2000

The universality of calcium as an intracellular messenger depends on its enormous versatility. Cells have a calcium signalling toolkit with many components that can be mixed and matched to create a wide range of spatial and temporal signals. This versatility is exploited to control processes as diverse as fertilization, proliferation, development, learning and memory, contraction and secretion, and must be accomplished within the context of calcium being highly toxic. Exceeding its normal spatial and temporal boundaries can result in cell death through both necrosis and apoptosis.

Metal Ions in Life Sciences, 2012

Proceedings of the National Academy of Sciences, 2002

An experiment performed in London nearly 120 years ago, which by today's standards would be considered unacceptably sloppy, marked the beginning of the calcium (Ca 2+ ) signaling saga. Sidney Ringer [Ringer, S. (1883) J. Physiol. 4, 29–43] was studying the contraction of isolated rat hearts. In earlier experiments, Ringer had suspended them in a saline medium for which he admitted to having used London tap water, which is hard: The hearts contracted beautifully. When he proceeded to replace the tap water with distilled water, he made a startling finding: The beating of the hearts became progressively weaker, and stopped altogether after about 20 min. To maintain contraction, he found it necessary to add Ca 2+ salts to the suspension medium. Thus, Ringer had serendipitously discovered that Ca 2+ , hitherto exclusively considered as a structural element, was active in a tissue that has nothing to do with bone or teeth, and performed there a completely novel function: It carried th...

The Biochemist, 2019

Calcium is an abundant alkaline earth metal. In the body, it is found as calcium ions (Ca2+), and most of it is deposited in hard tissues such as bones and teeth. But less well known is the role of Ca2+ as a messenger within cells. Here, I provide an overview of this hidden but critical function of Ca2+.

Biology of the Cell, 2004

Calcium is a ubiquitous second messenger controlling a broad range of cellular functions including growth and proliferation. Quiescent, hyperthrophic and proliferating cells have different types of calcium signal. In quiescent cells the calcium signal mostly involves elementary calcium events such as sparks and puffs, produced by localized Ca 2+ release via a cluster of intracellular calcium channels, IP3 receptors and ryanodine receptors. This type of calcium signal promotes activation of the transcription factor CREB (cAMP response element binding protein) leading to cell cycle arrest in G1 phase via transactivation of p53/p21 signaling pathways. Proliferation is induced by phosphoinositide-coupled agonists and is associated with a sustained increase in cytosolic calcium due to 1.) enhanced excitability of IP3Rs after IP3 binding; 2.) enhanced activity of store-operated Ca 2+ channels and T-type voltage-operated Ca 2+ channels; 3.) decreased cytosolic Ca 2+ removal due to inhibition of PMCA (plasma membrane Ca 2+ -ATPase) and SERCA (sarco/endoplasmic reticulum Ca 2+ -ATPase) calcium pumps. This type of calcium signal favors activation of the transcription factor NFAT (nuclear factor of activated T lymphocytes) that promotes hypertrophic growth and/or cell cycle progression. We suggest that the two main Ca 2+ -regulated transcription factors, CREB and NFAT, exert opposite control over cell growth and/or proliferation. Therapeutic strategies based on lowering intracellular Ca 2+ or targeting of Ca 2+regulated transcription factors seems to be a promising approach to arrest growth and/or proliferation.

Cellular Signalling, 2015

Cell proliferation is orchestrated through diverse proteins related to calcium (Ca 2+) signaling inside the cell. Cellular Ca 2+ influx occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca 2+ ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca 2+ from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca 2+ depletion in the endoplasmatic reticulum triggers Ca 2+ influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCE). SOCE is activated through a complex interplay between a Ca 2+ sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca 2+ channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation are discussed in this review.

Science China-life Sciences, 2011

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.

The Journal of General Physiology

Plant Science, 2001

Journal of Biosciences, 2007

Science China Life Sciences, 2012

As a highly versatile intracellular signal, calcium (Ca 2+) regulates many different cellular processes in both animal and plant systems. Disruption of Ca 2+ homeostasis contributes to several human diseases. Owing to the importance of Ca 2+ signalling, its research is now an active field in life science. There are numerous Ca 2+ signalling systems, consisting of a diverse array of signalling units that deliver Ca 2+ signals with different spatial and temporal properties [1,2], playing roles in ubiquitous biological processes including gene regulation, fuel generation, substance transport, hormone and neurotransmitter secretion, cell motility and muscle contraction [3]. Consequently, exquisite homeostasis of Ca 2+ cycling is the key for health of humans, the disruption of which is related to many human diseases such as heart failure, neuron-degeneration, and diabetes [46]. Many remarkable achievements have greatly enhanced our understanding of Ca 2+ signaling, including those from Chinese scientists [710]. The 17th International Symposium on Ca 2+-binding Proteins and Ca 2+ Function in Health and Disease was held in Beijing, China, on July 16-20, 2011 [11], accompany which, a special issue of Science China Life Sciences was published for transducing Ca 2+ signals to effectors. The first part focused on the mechanisms in maintaining a low cytosolic level of Ca 2+ , with two articles reviewing the properties of the plasma membrane calcium ATPases (PMCA) in ejecting Ca 2+ into the extracellular space. First, Carafoli [12] reviewed the role of the plasma membrane calcium pump, PMCA2, in the hearing process. As an im-Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Bioinformatics (Oxford, England), 2018

Ca2+ is a central second messenger in eukaryotic cells that regulates many cellular processes. Recently, we have indicated that typical Ca2+ signals are not purely oscillatory as widely assumed but exhibit stochastic spiking with cell type and pathway specific characteristics. Here, we present CaSiAn (Calcium Signaling Analyzer), an open source software tool that allows for quantifying these signal characteristics including individual spike properties and time course statistics in a semi-automated manner. CaSiAn provides an intuitive graphical user interface allowing experimentalists to easily process a large amount of Ca2+ signals, interactively tune peak detection, revise statistical measures and access the quantified signal properties as excel or text files. CaSiAn is implemented in Java and available on Github (https://github.com/mmahsa/CaSiAn) as well as on the project page (http://r3lab.uni.lu/web/casa). [email protected]. Supplementary data are available at Bioinformati...

Frontiers in Physiology, 2021

International Journal of Molecular Sciences, 2015

Calcium (Ca 2+) plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca 2+ is critically involved in the innervation of skeletal muscle fibers that results in the exertion of an action potential along the muscle fiber membrane, the prerequisite for skeletal muscle contraction. Furthermore and among others, Ca 2+ regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca 2+-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca 2+ ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca 2+ ions in adult muscle but also highlight recent findings of critical Ca 2+-dependent mechanisms essential for skeletal muscle-regulation and maintenance.