Store-Operated Calcium Entry Channels

Emerging Applications, Perspectives, and Discoveries in Cardiovascular Research - Advances in Medical Diagnosis, Treatment, and Care ◽

10.4018/978-1-5225-2092-4.ch004 ◽

2017 ◽

pp. 53-72

Author(s):

Diptiman D. Bose

Keyword(s):

Cardiac Function ◽

Immune Cells ◽

Cellular Functions ◽

Excitable Cells ◽

Extracellular Milieu ◽

Store Operated Calcium Entry ◽

Endoplasmic Reticulum Protein ◽

Cardiac Disorders ◽

Ca2 Channels

Store-operated Ca2+ entry (SOCE) channels mediate Ca2+ influx from the extracellular milieu into the cytosol to regulate a myriad of cellular functions. The Ca2+-release activated Ca2+ current has been well characterized in non-excitable cells such as immune cells. However, the role of SOCE proteins in cardiomyocytes and cardiac function has only been recently investigated. The localized endoplasmic reticulum protein, stromal interaction molecule (STIM) and plasma membrane Ca2+ channels, ORAI form the minimal functional unit of SOCE. The documentation of STIM and Orai expression in cardiomyocytes has raised questions regarding their role in cardiac function. Recent evidence supports the central role of STIM and Orai in gene transcription and, subsequent phenotypic changes associated with cardiac remodeling and hypertrophy. The purpose of this chapter is to provide an overview of our current understanding of SOCE proteins and, to explore their contributions to cardiovascular function and role in cardiac disorders.

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Evidence for an interaction between Golli and STIM1 in store-operated calcium entry

Biochemical Journal ◽

10.1042/bj20100650 ◽

2010 ◽

Vol 430 (3) ◽

pp. 453-460 ◽

Cited By ~ 45

Author(s):

Ciara M. Walsh ◽

Mary K. Doherty ◽

Alexei V. Tepikin ◽

Robert D. Burgoyne

Keyword(s):

Hela Cells ◽

Underlying Mechanism ◽

Binding Assays ◽

Cellular Functions ◽

Store Depletion ◽

Store Operated Calcium Entry ◽

Oligodendrocyte Precursor ◽

Ca2 Channels

SOCCs (store-operated Ca2+ channels) are highly selective ion channels that are activated upon release of Ca2+ from intracellular stores to regulate a multitude of diverse cellular functions. It was reported previously that Golli-BG21, a member of the MBP (myelin basic protein) family of proteins, regulates SOCE (store-operated Ca2+ entry) in T-cells and oligodendrocyte precursor cells, but the underlying mechanism for this regulation is unknown. In the present study we have discovered that Golli can directly interact with the ER (endoplasmic reticulum) Ca2+-sensing protein STIM1 (stromal interaction molecule 1). Golli interacts with the C-terminal domain of STIM1 in both in vitro and in vivo binding assays and this interaction may be modulated by the intracellular Ca2+ concentration. Golli also co-localizes with full-length STIM1 and Orai1 complexes in HeLa cells following Ca2+ store depletion. Overexpression of Golli reduces SOCE in HeLa cells, but this inhibition is overcome by overexpressing STIM1. We therefore suggest that Golli binds to STIM1–Orai1 complexes to negatively regulate the activity of SOCCs.

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Plasma Membrane and Organellar Targets of STIM1 for Intracellular Calcium Handling in Health and Neurodegenerative Diseases

Cells ◽

10.3390/cells10102518 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2518

Author(s):

Valentina Tedeschi ◽

Daniele La Russa ◽

Cristina Franco ◽

Antonio Vinciguerra ◽

Diana Amantea ◽

...

Keyword(s):

Plasma Membrane ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Transient Receptor Potential Channel ◽

Calcium Handling ◽

Cellular Functions ◽

Main Pathway ◽

Store Operated Calcium Entry ◽

Transient Receptor ◽

Ca2 Channels

Located at the level of the endoplasmic reticulum (ER) membrane, stromal interacting molecule 1 (STIM1) undergoes a complex conformational rearrangement after depletion of ER luminal Ca2+. Then, STIM1 translocates into discrete ER-plasma membrane (PM) junctions where it directly interacts with and activates plasma membrane Orai1 channels to refill ER with Ca2+. Furthermore, Ca2+ entry due to Orai1/STIM1 interaction may induce canonical transient receptor potential channel 1 (TRPC1) translocation to the plasma membrane, where it is activated by STIM1. All these events give rise to store-operated calcium entry (SOCE). Besides the main pathway underlying SOCE, which mainly involves Orai1 and TRPC1 activation, STIM1 modulates many other plasma membrane proteins in order to potentiate the influxof Ca2+. Furthermore, it is now clear that STIM1 may inhibit Ca2+ currents mediated by L-type Ca2+ channels. Interestingly, STIM1 also interacts with some intracellular channels and transporters, including nuclear and lysosomal ionic proteins, thus orchestrating organellar Ca2+ homeostasis. STIM1 and its partners/effectors are significantly modulated in diverse acute and chronic neurodegenerative conditions. This highlights the importance of further disclosing their cellular functions as they might represent promising molecular targets for neuroprotection.

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Store Operated Calcium Entry in Cell Migration and Cancer Metastasis

Cells ◽

10.3390/cells10051246 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1246

Author(s):

Ayat S. Hammad ◽

Khaled Machaca

Keyword(s):

Cell Migration ◽

Cancer Metastasis ◽

Cell Movement ◽

Excitable Cells ◽

Cellular Events ◽

Store Operated Calcium Entry ◽

Directional Cell Migration ◽

Multicellular Organisms ◽

Migrating Cells

Ca2+ signaling is ubiquitous in eukaryotic cells and modulates many cellular events including cell migration. Directional cell migration requires the polarization of both signaling and structural elements. This polarization is reflected in various Ca2+ signaling pathways that impinge on cell movement. In particular, store-operated Ca2+ entry (SOCE) plays important roles in regulating cell movement at both the front and rear of migrating cells. SOCE represents a predominant Ca2+ influx pathway in non-excitable cells, which are the primary migrating cells in multicellular organisms. In this review, we summarize the role of Ca2+ signaling in cell migration with a focus on SOCE and its diverse functions in migrating cells and cancer metastasis. SOCE has been implicated in regulating focal adhesion turnover in a polarized fashion and the mechanisms involved are beginning to be elucidated. However, SOCE is also involved is other aspects of cell migration with a less well-defined mechanistic understanding. Therefore, much remains to be learned regarding the role and regulation of SOCE in migrating cells.

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Calcium Signaling Regulates Autophagy and Apoptosis

Cells ◽

10.3390/cells10082125 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2125

Author(s):

Pramod Sukumaran ◽

Viviane Nascimento Da Conceicao ◽

Yuyang Sun ◽

Naseem Ahamad ◽

Luis R Saraiva ◽

...

Keyword(s):

Cell Survival ◽

Neuronal Development ◽

Critical Role ◽

Therapeutic Interventions ◽

Cellular Functions ◽

Excitable Cells ◽

Modulate Function ◽

Promote Cell Survival ◽

Regulatory Aspect

Calcium (Ca2+) 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/Ca2+ channels and Ca2+ storage in various organelles is critical in maintaining cytosolic Ca2+ levels that provide the spatial resolution needed for cellular homeostasis. An important regulatory aspect of Ca2+ homeostasis is a store operated Ca2+ entry (SOCE) mechanism that is activated by the depletion of Ca2+ from internal ER stores and has gained much attention for influencing functions in both excitable and non-excitable cells. Ca2+ has been shown to regulate opposing functions such as autophagy, that promote cell survival; on the other hand, Ca2+ 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 Ca2+ signaling in modulating these diverse functions in stem cell, immune regulation and neuromodulation.

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R93W Mutation in Orai1 Causes Impaired Calcium Influx in Platelets.

Blood ◽

10.1182/blood.v112.11.1838.1838 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1838-1838

Author(s):

Wolfgang Bergmeier ◽

Masatsugu Oh-hora ◽

Christie-Ann McCarl ◽

R. Claire Roden ◽

Paul F. Bray ◽

...

Keyword(s):

Calcium Influx ◽

Ex Vivo ◽

Cellular Responses ◽

Flow Conditions ◽

Excitable Cells ◽

Calcium Store ◽

Inactive Form ◽

Store Operated Calcium Entry ◽

Static Conditions

Abstract The intracellular Ca2+ concentration of non-excitable cells is regulated by calcium store release and store-operated calcium entry (SOCE). In platelets, STIM1 was recently identified as the main calcium sensor expressed in the endoplasmatic reticulum. To evaluate the role of the SOC channel moiety, Orai1, in platelet SOCE, we generated mice expressing a mutated, inactive form of Orai1 in blood cells only (Orai1R93W). Platelets expressing Orai1R93W were characterized by markedly reduced SOCE and impaired agonist-induced increases in [Ca2+]i. Orai1R93W platelets showed reduced integrin activation and impaired degranulation when stimulated with low agonist concentrations under static conditions. This defect, however, did not significantly affect the ability of Orai1R93W platelets to aggregate or to adhere to collagen under arterial flow conditions ex vivo. In contrast, these adherent Orai1R93W platelets were defective in surface phosphatidylserine exposure, suggesting that Orai1 is crucial for the platelets pro-coagulant response rather than for other Ca2+-dependent cellular responses.

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Protein partners of the calcium channel β subunit highlight new cellular functions

Biochemical Journal ◽

10.1042/bcj20160125 ◽

2016 ◽

Vol 473 (13) ◽

pp. 1831-1844 ◽

Cited By ~ 4

Author(s):

Mohamad Rima ◽

Marwa Daghsni ◽

Ziad Fajloun ◽

Ridha M'rad ◽

Juan L. Brusés ◽

...

Keyword(s):

Plasma Membrane ◽

Cell Signalling ◽

Β Subunit ◽

Cellular Functions ◽

Excitable Cells ◽

Functional Roles ◽

Physiological Processes ◽

Protein Partners ◽

Wide Range

Calcium plays a key role in cell signalling by its intervention in a wide range of physiological processes. Its entry into cells occurs mainly via voltage-gated calcium channels (VGCC), which are found not only in the plasma membrane of excitable cells but also in cells insensitive to electrical signals. VGCC are composed of different subunits, α1, β, α2δ and γ, among which the cytosolic β subunit (Cavβ) controls the trafficking of the channel to the plasma membrane, its regulation and its gating properties. For many years, these were the main functions associated with Cavβ. However, a growing number of proteins have been found to interact with Cavβ, emphasizing the multifunctional role of this versatile protein. Interestingly, some of the newly assigned functions of Cavβ are independent of its role in the regulation of VGCC, and thus further increase its functional roles. Based on the identity of Cavβ protein partners, this review emphasizes the diverse cellular functions of Cavβ and summarizes both past findings as well as recent progress in the understanding of VGCC.

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The Role of microRNAs in the Viral Infections

Current Pharmaceutical Design ◽

10.2174/1381612825666190110161034 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4659-4667 ◽

Cited By ~ 4

Author(s):

Mona Fani ◽

Milad Zandi ◽

Majid Rezayi ◽

Nastaran Khodadad ◽

Hadis Langari ◽

...

Keyword(s):

Viral Infections ◽

Rna Viruses ◽

Regulation Of Gene Expression ◽

Molecular Structures ◽

Main Function ◽

Cellular Functions ◽

Viral Genes ◽

Non Coding Rnas ◽

Post Transcriptional Regulation

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.

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PD-L1 Inhibitors for the Treatment of Prostate Cancer

Current Drug Targets ◽

10.2174/1389450121666200609142219 ◽

2020 ◽

Vol 21 (15) ◽

pp. 1558-1565

Author(s):

Matteo Santoni ◽

Francesco Massari ◽

Liang Cheng ◽

Alessia Cimadamore ◽

Marina Scarpelli ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Trials ◽

T Lymphocytes ◽

Chronic Inflammation ◽

Immune Cells ◽

Response To Therapy ◽

Complex Series

The carcinogenesis of prostate cancer (PCa) results from a complex series of events. Chronic inflammation and infections are crucial in this context. Infiltrating M2 type macrophages, as well as neutrophils and T lymphocytes, contribute to PCa development, progression and response to therapy. The preliminary findings on the efficacy of immunotherapy in patients with PCa were not encouraging. However, a series of studies investigating anti-PD-L1 agents such as Atezolizumab, Avelumab and Durvalumab used alone or in combination with other immunotherapies, chemotherapy or locoregional approaches are in course in this tumor. In this review, we illustrate the role of immune cells and PD-L1 expression during PCa carcinogenesis and progression, with a focus on ongoing clinical trials on anti-PD-L1 agents in this context.

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