Guangzhou Institute of Paediatrics, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou, Guangdong, 510623, China.
Next to T and B cells, natural killer (NK) cells are the third largest lymphocyte population. They are recently re-categorized as innate lymphocytes (ILCs), which also include ILC1, ILC2, ILC3, and the lymphoid tissue inducer (LTi) cells. Both NK cells and ILC1 cells are designated as group 1 ILCs because they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF). Read More
Telomeres at the ends of chromosomes safeguard genome integrity and stability in human nucleated cells. However, telomere repeats shed off during cell proliferation and other stress responses. Our recent studies show that telomere attrition induces not only epithelial stem cell senescence but also low-grade inflammation in the lungs. Read More
Toll-like receptors (TLRs) are one of the best characterised families of pattern recognition receptors (PRRs) and play a critical role in the host defence to infection. Accumulating evidence indicates that TLRs also participate in maintaining tissue homeostasis by controlling inflammation and tissue repair, as well as promoting antitumour effects via activation and modulation of adaptive immune responses. TLR agonists have successfully been exploited to ameliorate the efficacy of various cancer therapies. Read More
Stimulator of interferon (IFN) genes (STING) is a key mediator in the immune response to cytoplasmic DNA sensed by cyclic GMP-AMP (cGAMP) synthase (cGAS). After synthesis by cGAS, cGAMP acts as a second messenger activating STING in the cell harboring cytoplasmic DNA but also in adjacent cells through gap junction transfer. While the role of the cGAS-STING pathway in pathogen detection is now well established, its importance in cancer immunity has only recently started to emerge. Read More
Department of Medicine, St George & Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Australia, Level 2 Clinical Sciences (WR Pitney) Building, St George Hospital, Short St, Kogarah, NSW, 2217, Australia.
The intestinal microbes form a symbiotic relationship with their human host to harvest energy for themselves and their host and to shape the immune system of their host. However, alteration of this relationship, which is named as a dysbiosis, has been associated with the development of different inflammatory diseases and cancers. It is found that metabolites, cellular components, and virulence factors derived from the gut microbiota interact with the host locally or systemically to modulate the dysbiosis and the development of these diseases. Read More
CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Life Science Research Building B-205, Shanghai, 200031, China.
Inflammasomes are critical checkpoints in inflammation. The activation of inflammasome can cause a series of inflammatory responses including maturation of interleukin (IL)-1β and IL-18 and a specialized form of cell death called pyroptosis. Since its identification in the early 2000s, inflammasomes have been implicated to play multifaceted roles in varied pathological and physiological conditions, especially in the mucosal compartments including the gut. Read More
Hudson Institute of Medical Research, Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, 3168, Australia.
microRNAs play a fundamental role in the immune system. One particular microRNA, miR-155 plays a critical role in hematopoietic cell development and tightly regulates innate and adaptive immune responses in response to infection. However, its dysregulation, more specifically its overexpression, is closely associated with various inflammatory disorders. Read More
Histone deacetylases (HDACs) are an emerging class of molecules involved in the epigenetic regulation of innate immune responses through Toll-like receptor (TLR) and interferon (IFN) signaling pathways. HDACs are also key drivers of inflammatory diseases via epigenetic regulation through chromatin DNA and histone modification by methylation and acetylation, among other mechanisms, which control innate immune cell gene expression. Importantly, these epigenetic changes are reversible, and HDACs may also be targeted by small-molecule HDAC inhibitors, which have been used in clinical settings for cancer therapy. Read More
Macrophages and dendritic cells initiate the innate immune response to infection and injury and contribute to inflammatory signaling to maintain the homeostasis of various tissues, which includes resident macrophages for the elimination of invading microorganisms and tissue damage. Inappropriate inflammatory signaling can lead to persistent inflammation and further develop into autoimmune and inflammation-associated diseases. Inflammatory signaling pathways have been well characterized, but how these signaling pathways are converted into sustained and diverse patterns of expression of cytokines, chemokines, and other genes in response to environmental challenges is unclear. Read More
Inflammation is usually the defensive reaction of the immune system to the invasion of pathogen and the exogenous objects. The activation of inflammation helps our body to eliminate pathogenic microbe, virus, and parasite harming our health, while under many circumstances inflammation is the direct cause of the pathological damage in tissues and dysfunction of organs. The posttranslational modification (PTM) of the inflammatory pathways, such as TLR pathways, RLR pathways, NLR pathway, intracellular DNA sensors, intracellular RNA sensors, and inflammasomes, is crucial in the regulation of these signaling trails. Read More
The families of innate immune receptors are the frontline responders to danger. These superheroes of the host immune systems populate innate immune cells, surveying the extracellular environment and the intracellular endolysosomal compartments and cytosol for exogenous and endogenous danger signals. As a collective the innate immune receptors recognise a wide array of stimuli, and in response they initiate specific signalling pathways leading to activation of transcriptional or proteolytic pathways and the production of inflammatory molecules to destroy foreign pathogens and/or resolve tissue injury. Read More
P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. The platelet ADP-receptor which has been denominated P2Y12 receptor is an important target in pharmacotherapy. The receptor couples to Gαi2 mediating an inhibition of cyclic AMP accumulation and additional downstream events including the activation of phosphatidylinositol-3-kinase and Rap1b proteins. Read More
Cohort studies are observational studies in which the investigator determines the exposure status of subjects and then follows them for subsequent outcomes. The incidence of outcomes is observed in the exposed group and compared with that in a nonexposed group. Recently, new epidemiologic strategies have encouraged cohort research information exchange and cooperation to improve the cognition of disease etiology, such as case-cohort design and nested case-control study, which is available for "omics" data. Read More
The occurrence and progression of diseases are strongly associated with a combination of genetic, lifestyle, and environmental factors. Understanding the interplay between genetic and nongenetic components provides deep insights into disease pathogenesis and promotes personalized strategies for people healthcare. Recently, the paradigm of systems medicine, which integrates biomedical data and knowledge at multidimensional levels, is considered to be an optimal way for disease management and clinical decision-making in the era of precision medicine. Read More
While traditional nutrition science is focusing on nourishing population, modern nutrition is aiming at benefiting individual people. The goal of modern nutritional research is to promote health, prevent diseases, and improve performance. With the development of modern technologies like bioinformatics, metabolomics, and molecular genetics, this goal is becoming more attainable. Read More
Metabolic syndrome as a consequence of the association to overweight, hypertension, and diabetes is at high risk of coronary events. Regular physical training has been recently promoted to reduce cardiovascular risks factors, by the improved lifestyle and also by the "anti-inflammatory effectiveness." A positive impact has been shown in case of cancer survived patients either with or without comorbidities and especially in those subjects where the inflammatory process is globally represented. Read More
Computer-aided diagnosis provides a medical procedure that assists physicians in interpretation of medical images. This work focuses on computer-aided tongue image analysis specifically, based on Traditional Chinese Medicine (TCM). Tongue diagnosis is an important component of TCM. Read More
College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, Guangdong Province, People's Republic of China.
Biological trace elements are essential for human health. Imbalance in trace element metabolism and homeostasis may play an important role in a variety of diseases and disorders. While the majority of previous researches focused on experimental verification of genes involved in trace element metabolism and those encoding trace element-dependent proteins, bioinformatics study on trace elements is relatively rare and still at the starting stage. Read More
As newborn screening success stories gained general confirmation during the past 50 years, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. Outstanding progress in sequencing technologies over the last two decades has made it possible to comprehensively profile newborn screening (NBS) and identify clinically relevant genomic alterations. With the rapid developments in whole-genome sequencing (WGS) and whole-exome sequencing (WES) recently, we can detect newborns at the genomic level and be able to direct the appropriate diagnosis to the different individuals at the appropriate time, which is also encompassed in the concept of precision medicine. Read More
Advancement in technology has nurtured the new era of genetic tests for personalized medicine. In this chapter, we will introduce the current development, challenges, and the outlook of genetic test, disease risk prediction, and genetic counseling. In the first section, we will present the success cases in the areas of molecular classification of tumors, pharmacogenomics, and Mendelian disorders, and the challenges of genetic tests implementations. Read More
Center for Systems Biology, Soochow University, No.1 Shizi Street, Suzhou, Jiangsu, 215006, China.
The past decade has witnessed great advances in biomedical informatics. Biomedical informatics is an emerging field of healthcare that aims to translate the laboratory observation into clinical practice. Smart healthcare has also developed rapidly with ubiquitous sensor and communication technologies. Read More
The study investigated a panel of lysosomal enzymes in the liver and kidney tissues in alloxan-induced diabetes in the mouse. The mice were divided into six experimental groups receiving 10% alloxan at a dose of 50 and 75 mg/kg over a period of four, eight, and twelve days; each group was compared with controls receiving 0.9% NaCl. Read More
Inserm U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Université de Sciences et Technologies de Lille (USTL), 59655, Villeneuve d'Ascq, France.
Store-operated calcium entry (SOCE) plays important roles in a multitude of cellular processes, from muscle contraction to cellular proliferation and migration. Dysregulation of SOCE is responsible for the advancement of multiple diseases, ranging from immune diseases, myopathies, to terminal ones like cancer. Naturally, SOCE has been a focus of many studies and review papers which, however, primarily concentrated on the principal players localized to the plasma membrane and responsible for Ca(2+) entry into the cell. Read More
In steatotic hepatocytes, intracellular Ca(2+) homeostasis is substantially altered compared to normal. Decreased Ca(2+) in the endoplasmic reticulum (ER) can lead to ER stress, an important mediator of the progression of liver steatosis to nonalcoholic steatohepatitis, type 2 diabetes, and hepatocellular carcinoma. Store-operated Ca(2+) channels (SOCs) in hepatocytes are composed principally of Orai1 and STIM1 proteins. Read More
At the time of fertilization, the sperm activates the egg and induces embryonic development by triggering an elevation in the egg's intracellular free Ca(2+) concentration. In mammals the initial Ca(2+) rise is followed by a series of repetitive Ca(2+) transients (known as oscillations) that last for several hours. Although the source of Ca(2+) during the signaling process is primarily the egg's smooth endoplasmic reticulum, the oscillations stop in the absence of extracellular Ca(2+) indicating that a Ca(2+) influx across the plasma membrane is essential to sustain them. Read More
Department of Cell Physiology and Metabolism, University of Geneva, 1 rue Michel Servet, 1211, Geneva, Switzerland.
Transient receptor potential canonical (TRPC) channels belong to the large family of TRPs that are mostly nonselective cation channels with a great variety of gating mechanisms. TRPC are composed of seven members that can all be activated downstream of agonist-induced phospholipase C stimulation, but some members are also stretch-activated and/or are part of the store-operated Ca(2+) entry (SOCE) pathway. Skeletal muscles generate contraction via an explosive increase of cytosolic Ca(2+) concentration resulting almost exclusively from sarcoplasmic reticulum Ca(2+) channel opening. Read More
Calcium (Ca(2+)) is a ubiquitous second messenger that performs significant physiological task such as neurosecretion, exocytosis, neuronal growth/differentiation, and the development and/or maintenance of neural circuits. An important regulatory aspect of neuronal Ca(2+) homeostasis is store-operated Ca(2+) entry (SOCE) which, in recent years, has gained much attention for influencing a variety of nerve cell responses. Essentially, activation of SOCE ensues following the activation of the plasma membrane (PM) store-operated Ca(2+) channels (SOCC) triggered by the depletion of endoplasmic reticulum (ER) Ca(2+) stores. Read More
Inserm UMR S1180, University Paris-Sud, Université Paris-Saclay, 92296, Châtenay-Malabry, France.
For a long time, Ca(2+) entry into cardiomyocytes was considered the sole domain of the L-type Ca(2+) channel. Recently, STIM1/Orai1-mediated store-operated Ca(2+) entry has been also reported to participate to Ca(2+) influx in cardiac cells and has emerged as a key player to alter Ca(2+) in the cardiomyocyte. In this review, we will highlight accumulated knowledge about the presence and the potential contribution of STIM1/Orai1-dependent SOCE to cardiac function and its role in the cardiac pathogenesis. Read More
Department of Internal Medicine I, Comprehensive Heart Failure Center Würzburg, University Hospital Würzburg, Würzburg, Germany.
TRPC channels have been suggested as potential candidates mediating store-operated Ca(2+) entry (SOCE) in cardiomyocytes. There is increasing evidence that the TRPC isoforms TRPC1 and TRPC4 might fulfill the function as SOCs, in concert with or in parallel to the key players of SOCE, Orai1, and STIM1. Several other isoforms, e. Read More
The discovery of the store-operated Ca(2+) entry (SOCE) phenomenon is tightly associated with its recognition as a pathway of high (patho)physiological significance in the cardiovascular system. Early on, SOCE has been investigated primarily in non-excitable cell types, and the vascular endothelium received particular attention, while a role of SOCE in excitable cells, specifically cardiac myocytes and pacemakers, was initially ignored and remains largely enigmatic even to date. With the recent gain in knowledge on the molecular components of SOCE as well as their cellular organization within nanodomains, potential tissue/cell type-dependent heterogeneity of the SOCE machinery along with high specificity of linkage to downstream signaling pathways emerged for cardiovascular cells. Read More
Cell Physiology Research Group, Department of Physiology, University of Extremadura, Cáceres, Spain.
Among the Ca(2+) entry mechanisms in platelets, store-operated Ca(2+) entry (SOCE) plays a prominent role as it is necessary to achieve full activation of platelet functions and replenish intracellular Ca(2+) stores. In platelets, as in other non-excitable cells, SOCE has been reported to involve the activation of plasma membrane channels by the ER Ca(2+) sensor STIM1. Despite electrophysiological studies are not possible in human platelets, indirect analyses have revealed that the Ca(2+)-permeable channels involve Orai1 and, most likely, TRPC1 subunits. Read More
Store-operated Ca(2+) entry (SOCE) mediated by STIM and Orai proteins is a highly regulated and ubiquitous signaling pathway that plays an important role in various cellular and physiological functions. Endoplasmic reticulum (ER) serves as the major site for intracellular Ca(2+) storage. Stromal Interaction Molecule 1/2 (STIM1/2) sense decrease in ER Ca(2+) levels and transmits the message to plasma membrane Ca(2+) channels constituted by Orai family members (Orai1/2/3) resulting in Ca(2+) influx into the cells. Read More
Department of Physiology, David Geffen School of Medicine at UCLA, 53-266 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA.
Engagement of T cell receptors (TCRs) with cognate antigens triggers cascades of signaling pathways in helper T cells. TCR signaling is essential for the effector function of helper T cells including proliferation, differentiation, and cytokine production. It also modulates effector T cell fate by inducing cell death, anergy (nonresponsiveness), exhaustion, and generation of regulatory T cells. Read More
Cell Physiology Research Group, Department of Physiology, University of Extremadura, Cáceres, Spain.
Since store-operated Ca(2+) entry (SOCE) was proposed by Putney three decades ago (Putney. Cell Calcium 7:1-12, 1986), its functional role and involvement in the pathophysiology of a number of disorders has been investigated. The role of SOCE in cell physiology has been discussed in the previous chapters, and the following part is devoted to the current knowledge concerning the mechanisms underlying the development of certain diseases that involve SOCE abnormalities. Read More
Calcium (Ca(2+)) is a key regulator of cardiomyocyte contraction. The Ca(2+) channels, pumps, and exchangers responsible for the cyclical cytosolic Ca(2+) signals that underlie contraction are well known. In addition to those Ca(2+) signaling components responsible for contraction, it has been proposed that cardiomyocytes express channels that promote the influx of Ca(2+) from the extracellular milieu to the cytosol in response to depletion of intracellular Ca(2+) stores. Read More
Many cellular functions of the vascular endothelium are regulated by fine-tuned global and local, microdomain-confined changes of cytosolic free Ca(2+) ([Ca(2+)]i). Vasoactive agonist-induced stimulation of vascular endothelial cells (VECs) typically induces Ca(2+) release through IP3 receptor Ca(2+) release channels embedded in the membrane of the endoplasmic reticulum (ER) Ca(2+) store, followed by Ca(2+) entry from the extracellular space elicited by Ca(2+) store depletion and referred to as capacitative or store-operated Ca(2+) entry (SOCE). In vascular endothelial cells, SOCE is graded with the degree of store depletion and controlled locally in the subcellular microdomain where depletion occurs. Read More
In this chapter we examine the importance of cytoplasmic nanojunctions-nanometer scale appositions between organellar membranes including the molecular transporters therein-to the cell signaling machinery, with specific reference to Ca(2+) transport and signaling in vascular smooth muscle and endothelial cells. More specifically, we will consider the extent to which quantitative modeling may aid in the development of our understanding of these processes. Testament to the requirement for such approaches lies in the fact that recent studies have provided evermore convincing evidence in support of the view that cytoplasmic nanospaces may be as significant to the process of Ca(2+) signaling as the Ca(2+) transporters, release channels, and Ca(2+)-storing organelles themselves. Read More
Institute of Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstrasse 6/6, 8010, Graz, Austria.
In most cell types, the depletion of internal Ca(2+) stores triggers the activation of Ca(2+) entry. This crucial phenomenon is known since the 1980s and referred to as store-operated Ca(2+) entry (SOCE). With the discoveries of the stromal-interacting molecules (STIMs) and the Ca(2+)-permeable Orai channels as the long-awaited molecular constituents of SOCE, the role of mitochondria in controlling the activity of this particular Ca(2+) entry pathway is kind of buried in oblivion. Read More
Store-operated Ca(2+) entry (SOCE) is a cell signaling pathway essential for immune and muscle function controlled by dynamic interactions between Ca(2+)-sensing STIM proteins on the endoplasmic reticulum (ER) and Ca(2+)-permeable ORAI channels on the plasma membrane (PM). STIM-ORAI interactions occur at membrane contact sites (MCS), evolutionarily conserved cellular structures characterized by the close apposition (10-20 nm) between the ER and target membranes that facilitate the exchange of lipids by non-vesicular transport mechanisms. STIM-ORAI interactions were considered to be restricted to ER-PM MCS, but recent evidence indicates that productive interactions take place between ER-bound STIM1 and Ca(2+) channels located in intracellular organelles. Read More
Mitochondria extensively modify virtually all cellular Ca(2+) transport processes, and store-operated Ca(2+) entry (SOCE) is no exception to this rule. The interaction between SOCE and mitochondria is complex and reciprocal, substantially altering and, ultimately, fine-tuning both capacitative Ca(2+) influx and mitochondrial function. Mitochondria, owing to their considerable Ca(2+) accumulation ability, extensively buffer the cytosolic Ca(2+) in their vicinity. Read More
Transient receptor potential canonical (TRPC) proteins were identified as molecular candidates of receptor- and/or store-operated channels because of their close homology to the Drosophila TRP and TRPL. Functional studies have revealed that TRPC channels play an integrated part of phospholipase C-transduced cell signaling, mediating the influx of both Ca(2+) and Na(+) into cells. As a consequence, the TRPC channels have diverse functional roles in different cell types, including metabotropic receptor-evoked membrane depolarization and intracellular Ca(2+) concentration elevation. Read More
The Physiological Laboratory, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, The University of Liverpool, Crown Street, Liverpool, L69 3BX, UK.
The junctions between the endoplasmic reticulum and the plasma membrane are essential platforms for the activation of store-operated Ca(2+) influx. These junctions have specific dimensions and are nonuniformly distributed in polarized cells. The mechanisms involved in the formation of the junctions are currently undergoing vigorous investigation, and significant progress was attained in this research area during the last 10 years. Read More
In the title of this part of the book, the tail is wagging not just in a single dog but multiple dogs; in other words, a single process SOCE (tail) somehow involves a cross talk of (wagging) large and powerful organelle and cellular compartments (dogs). So how is this possible? Is this really necessary? Is the title actually appropriate?SOCE is a rather special process, it allows efficient signaling based on a ubiquitous second messenger (Ca(2+)) in multiple cell and tissue types, it has specific signaling modality (i.e. Read More
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, México, DF, 04510, Mexico.
The basic paradigm of a mechanism for calcium influx triggered after a reduction on calcium store content implies a sensor of calcium concentration on the endoplasmic reticulum (the stores) and a calcium channel immersed on the plasma membrane. These two basic components are STIM and Orai, the most fundamental and minimal molecular constituents of the store-operated calcium entry mechanism. However, even when minimal components can be reduced to these two proteins, the intricate process involved in approximating two cellular membranes (endoplasmic reticulum, ER and plasma membrane, PM) require the participation of several other components, many of which remain unidentified to this date. Read More
Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research - NIDCR, National Institutes of Health - NIH, Building 10, Room 1N-113, Bethesda, MD, 20892, USA.
Store-operated calcium entry (SOCE) is a ubiquitous Ca(2+) entry pathway that is activated in response to depletion of ER-Ca(2+) stores and critically controls the regulation of physiological functions in a wide variety of cell types. The transient receptor potential canonical (TRPC) channels (TRPCs 1-7), which are activated by stimuli leading to PIP2 hydrolysis, were first identified as molecular components of SOCE channels. While TRPC1 was associated with SOCE and regulation of function in several cell types, none of the TRPC members displayed I CRAC, the store-operated current identified in lymphocytes and mast cells. Read More
Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research - NIDCR, National Institute of Health, Building 10, Room 1N-112, Bethesda, MD, 20892, USA.
Ca(2+) influx by plasma membrane Ca(2+) channels is the crucial component of the receptor-evoked Ca(2+) signal. The two main Ca(2+) influx channels of non-excitable cells are the Orai and TRPC families of Ca(2+) channels. These channels are activated in response to cell stimulation and Ca(2+) release from the endoplasmic reticulum (ER). Read More
Ca(2+) signals regulate a plethora of cellular functions that include muscle contraction, heart beating, hormone secretion, lymphocyte activation, gene expression, and metabolism. To study the impact of Ca(2+) signals on biological processes, pharmacological tools and caged compounds have been commonly applied to induce fluctuations of intracellular Ca(2+) concentrations. These conventional approaches, nonetheless, lack rapid reversibility and high spatiotemporal resolution. Read More
Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine, Saarland University, Homburg, Germany.
Cysteines are among the least abundant amino acids found in proteins. Due to their unique nucleophilic thiol group, they are able to undergo a broad range of chemical modifications besides their known role in disulfide formation, such as S-sulfenylation (-SOH), S-sulfinylation (-SO(2)H), S-sufonylation (-SO(3)H), S-glutathionylation (-SSG), and S-sulfhydration (-SSH), among others. These posttranslational modifications can be irreversible and act as transitional modifiers or as reversible on-off switches for the function of proteins. Read More
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
Store-operated Ca(2+) entry fulfills a crucial role in controlling Ca(2+) signals in almost all cells. The Ca(2+)-sensing stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER) undergo complex conformational changes in response to depleted ER luminal Ca(2+), allowing them to unfold and become trapped in ER-plasma membrane (PM) junctions. Dimers of STIM proteins trap and gate the plasma membrane Orai Ca(2+) channels within these junctions to generate discrete zones of high Ca(2+) and regulate sensitive Ca(2+)-dependent intracellular signaling pathways. Read More
Institute of Biophysics, Johannes Kepler University Linz, 4020, Linz, Austria.
A primary Ca(2+) entry pathway in non-excitable cells is established by the Ca(2+) release-activated Ca(2+) channels. Their two limiting molecular components include the Ca(2+)-sensor protein STIM1 located in the endoplasmic reticulum and the Orai channel in the plasma membrane. STIM1 senses the luminal Ca(2+) content, and store depletion induces its oligomerization into puncta-like structures, thereby triggering coupling to as well as activation of Orai channels. Read More