Store-Operated Calcium Channels

Parekh, Anant B.; Putney, James W.

doi:10.1152/physrev.00057.2003

Cited by 1,909 publications

(1,945 citation statements)

References 415 publications

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“…Receptor-mediated release of Ca 2+ from intracellular stores induces Ca 2+ entry through calcium release-activated calcium (CRAC) channels [5][6][7] . Previous studies have identified STIM1 as the potential sensor for endoplasmic reticulum luminal Ca 2+ concentration 1,8,9 .…”

Section: Introductionmentioning

confidence: 99%

“…Here, we show that STIM1 and CRACM1 interact functionally. Overexpression of both proteins greatly potentiates I CRAC , suggesting that STIM1 and CRACM1 mutually limit store-operated currents and that CRACM1 may be the long-sought CRAC channel.Receptor-mediated release of Ca 2+ from intracellular stores induces Ca 2+ entry through calcium release-activated calcium (CRAC) channels [5][6][7] . Previous studies have identified STIM1 as the potential sensor for endoplasmic reticulum luminal Ca 2+ concentration 1,8,9 .…”

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confidence: 99%

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Amplification of CRAC current by STIM1 and CRACM1 (Orai1)

et al. 2006

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Depletion of intracellular calcium stores activates store-operated calcium entry across the plasma membrane in many cells. STIM1, the putative calcium sensor in the endoplasmic reticulum, and the calcium release-activated calcium (CRAC) modulator CRACM1 (also known as Orai1) in the plasma membrane have recently been shown to be essential for controlling the store-operated CRAC current (I CRAC ) [1][2][3][4] . However, individual overexpression of either protein fails to significantly amplify I CRAC . Here, we show that STIM1 and CRACM1 interact functionally. Overexpression of both proteins greatly potentiates I CRAC , suggesting that STIM1 and CRACM1 mutually limit store-operated currents and that CRACM1 may be the long-sought CRAC channel.Receptor-mediated release of Ca 2+ from intracellular stores induces Ca 2+ entry through calcium release-activated calcium (CRAC) channels [5][6][7] . Previous studies have identified STIM1 as the potential sensor for endoplasmic reticulum luminal Ca 2+ concentration 1,8,9 . When Ca 2+ is depleted from intracellular stores, STIM1 translocates to vesicular structures (punctae) underneath the plasma membrane, where it is hypothesized to activate CRAC channels residing in the plasma membrane. A second protein, CRACM1, has recently been identified as essential for activating CRAC channels 3,4 . This protein contains four transmembrane domains, is located in the plasma membrane and, therefore, may represent the CRAC channel itself, a subunit of the channel, or a regulatory molecule that couples to the channel. When overexpressed individually, neither STIM1 nor CRACM1 can significantly potentiate I CRAC 1-4 .To address the potential interaction of STIM1 and CRACM1, both proteins were overexpressed individually, or in combination, in HEK293 and Jurkat T cells and the CRAC (Fig. 1b, d). Consistent with previous work 1,9 , overexpression of STIM1 alone caused a small-to-modest increase in I CRAC in HEK293 and Jurkat cells (Fig. 1a, c). CRACM1 overexpression alone did not affect the CRAC currents induced by store depletion in HEK293 cells (Fig. 1a, b) and caused a small reduction in I CRAC in Jurkat cells (Fig. 1c, d). Unless simply due to a general effect of transfection or variability of I CRAC across preparations, this reduction may be due to some kind of dominant-negative effect. Taken together, the available data on CRACM1 and STIM1 suggest that the individually expressed proteins, although essential for I CRAC manifestation, cannot significantly amplify the current. This would indicate that these proteins are either not sufficient to generate large CRAC currents or that they are stoichiometrically linked and limit each others' ability to generate CRAC currents above normal. Therefore, we co-overexpressed both proteins in HEK293 cells (see Supplementary Information, Fig. S1) and assessed store-operated currents by patch clamp. HHS Public AccessThe co-overexpression of STIM1 and CRACM1, in both HEK293 and Jurkat cells, is sufficient to generate enormous membrane currents ...

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Amplification of CRAC current by STIM1 and CRACM1 (Orai1)

et al. 2006

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“…This Ca 2+ entry pathway is a common and ubiquitous mechanism regulating Ca 2+ influx into cells (Putney 2011). In both excitable and non-excitable cells, SOCE regulates diverse cellular functions ranging from cell proliferation and gene expression to cell contraction and secretion (Berridge et al 2003;Parekh and Putney 2005;Venkatachalam et al 2002). Over the past decade, we (Ma et al 2000 and others (Mene et al 1994) have found that SOCE plays a role in Ca 2+ influx stimulated by agonists in human glomerular mesangial cells (GMCs).…”

Section: Introductionmentioning

confidence: 99%

Attenuated mesangial cell proliferation related to store-operated Ca2+ entry in aged rat: the role of STIM 1 and Orai 1

Shen

Zhu

Zhang

et al. 2013

AGE

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Store-operated Ca 2+ entry (SOCE) is a common and ubiquitous mechanism regulating Ca 2+ influx into cells and participates in numerous biological processes including cell proliferation. Glomerular mesangial cells (GMCs) play a role in the regulation of the glomerular filtration rate. From a clinical point of view, many physiological functions alter with age. In the present study, we used angiotensin II, glucagon, and the sarco/endoplasmic reticulum membrane Ca 2+ pump inhibitor thapsigargin to deplete the internal Ca 2+ stores for the activation of SOCE. We found that SOCE was significantly attenuated in GMCs from aged (22-month-old) rats. The expression of SOCErelated components, stromal interaction molecule 1 (STIM 1) and Orai 1, in freshly isolated glomeruli notably decreased, and STIM 1 and Orai 1 puncta formation significantly reduced in primary-cultured GMCs in aged rats. Moreover, specific knockdown of STIM 1 and Orai 1 by small interfering RNA markedly suppressed SOCE and cell proliferation of GMCs isolated from young (3-month-old) rats. We conclude that the attenuation of GMCs proliferation can be attributed to the decreased SOCE partially caused by reduced expression of STIM 1 and Orai 1.

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“…By contributing to cytosolic Ca 2+ elevation and to the replenishment of the ER Ca 2+ compartment [2,3], SOCE is a key regulator of many Ca 2+ dependent physiological processes [4]. Under physiological conditions, SOCE is induced by the activation of cell surface receptors coupled to e.g.…”

Section: Introductionmentioning

confidence: 99%

Thapsigargin activates Ca2+ entry both by store-dependent, STIM1/Orai1-mediated, and store-independent, TRPC3/PLC/PKC-mediated pathways in human endothelial cells

et al. 2011

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a b s t r a c tThe ER Ca 2+ sensor STIM1 and the Ca 2+ channel Orai1 are key players in store-operated Ca 2+ entry (SOCE). In addition, channels from the TRPC family were also shown to be engaged during SOCE, while their precise implication remains controversial. In this study, we investigated the molecular players involved in SOCE triggered by the SERCA pump inhibitor thapsigargin in an endothelial cell line, the EA.hy926. siRNA directed against STIM1 or Orai1 reduced Ca 2+ entry by about 50-60%, showing that a large part of the entry is independent from these proteins. Blocking the PLC or the PKC pathway completely abolished thapsigargin-induced Ca 2+ entry in cells depleted from STIM1 and/or Orai1. The phorbol ester PMA or the DAG analog OAG restored the Ca 2+ entry inhibited by PLC blockers, showing an involvement of PLC/PKC pathway in SOCE. Using pharmacological inhibitors or siRNA revealed that the PKCeta is required for Ca 2+ entry, and pharmacological inhibition of the tyrosine kinase Src also reduced Ca 2+ entry. TRPC3 silencing diminished the entry by 45%, while the double STIM1/TRPC3 invalidation reduced Ca 2+ entry by more than 85%. Hence, in EA.hy926 cells, TG-induced Ca 2+ entry results from the activation of the STIM1/Orai1 machinery, and from the activation of TRPC3.

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Store-Operated Calcium Channels

Cited by 1,909 publications

References 415 publications

Amplification of CRAC current by STIM1 and CRACM1 (Orai1)

Amplification of CRAC current by STIM1 and CRACM1 (Orai1)

Attenuated mesangial cell proliferation related to store-operated Ca2+ entry in aged rat: the role of STIM 1 and Orai 1

Thapsigargin activates Ca2+ entry both by store-dependent, STIM1/Orai1-mediated, and store-independent, TRPC3/PLC/PKC-mediated pathways in human endothelial cells

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