Store-Operated Calcium Channels

Prakriya, Murali; Lewis, Richard S.

doi:10.1152/physrev.00020.2014

Cited by 1,005 publications

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References 479 publications

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confidence: 99%

The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca²⁺-dependent inactivation

Mullins¹,

Lewis²

2016

J Cell Biol

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Ca 2+ release-activated Ca 2+ (CRAC) channels are prototypic store operated channels that are encoded by the Orai family of plasma membrane proteins and activated by depletion of Ca 2+ from the ER (Prakriya and Lewis, 2015). The ER protein STIM1 is best recognized for its function in sensing ER Ca 2+ depletion and, in response, activating CRAC channels in the plasma membrane. However, an early clue that STIM1 is more than an activating ligand for Orai1 was the observation that channels activated by an isolated fragment of STIM1 (the CRAC activation domain or CAD; STIM1 aa 342-448), failed to show characteristic fast Ca 2+ -dependent inactivation (CDI) in response to Ca 2+ entry . A series of C-terminal truncations identified a region of STIM1 (aa 470-491) that is required for CDI, termed the inactivation domain of STIM, or ID STIM . Additional evidence for a role of STIM1 in CDI came from observations that in heterologous systems the STIM1/Orai1 expression ratio influences the extent of CDI, with a ratio of 2-4:1 being Correspondence to Richard S. Lewis: r s l e w i s @ s t a n f o r d . e d u ; or Franklin M. Mullins: f m u l l i n s @ s t a n f o r d . e d u Abbreviations used in this paper: CDI, Ca 2+ -dependent inactivation; CRAC, Ca 2+ release-activated Ca 2+ ; DVF, divalent-free; ID STIM , inactivation domain of STIM.required for CDI to approach the level seen for native CRAC channels (Scrimgeour et al., 2009;Hoover and Lewis, 2011).A highly negatively charged region within ID STIM ( 475 DDVDDMDEE 483 ) attracted attention from several groups as a potential Ca 2+ binding site for CDI, based on analogy to the highly acidic Ca 2+ bowl binding site of the BK channel (Cox, 2011). Consistent with such a role, alanine or glycine substitutions for various combinations of acidic residues within this region reduced CDI, and full neutralization of all acidic residues eliminated CDI (Derler et al., 2009b;Lee et al., 2009;Mullins et al., 2009 The inactivation domain of STIM1 (ID STIM : amino acids 470-491) has been described as necessary for Ca 2+ -dependent inactivation (CDI) of Ca 2+ release-activated Ca 2+ (CRAC) channels, but its mechanism of action is unknown. Here we identify acidic residues within ID STIM that control the extent of CDI and examine functional interactions of ID STIM with Orai1 pore residues W76 and Y80. Alanine scanning revealed three ID STIM residues (D476/D478/ D479) that are critical for generating full CDI. Disabling ID STIM by a triple alanine substitution for these three residues ("STIM1 3A") or by truncation of the entire domain (STIM1 1-469 ) reduced CDI to the same residual level observed for the Orai1 pore mutant W76A (approximately one third of the extent seen with full-length STIM1). Results of noise analysis showed that STIM1 1-469 and Orai1 W76A mutants do not reduce channel open probability or unitary Ca 2+ conductance, factors that determine local Ca 2+ accumulation, suggesting that they diminish CDI instead by inhibiting the CDI gating mechanism. We tested for functional coupli...

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The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca²⁺-dependent inactivation

Mullins¹,

Lewis²

2016

J Cell Biol

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“…STIM1 functions as an ER Ca 2+ sensor, and Orai1 is a pore subunit located on the plasma membrane 48. Although there exist arguments on whether TRPC1 is a component of SOCE channel,49 our recent results from human cardiac c‐Kit + progenitor cells13 support the notion that TRPC1 works together with Orai1 to form discrete STIM1‐gated SOCE channel, mediate distinct Ca 2+ signals and regulate specific cellular functions 50, 51, 52…”

Section: Discussionmentioning

confidence: 81%

Bradykinin‐mediated Ca²⁺ signalling regulates cell growth and mobility in human cardiac c‐Kit⁺ progenitor cells

Che

et al. 2018

J Cellular Molecular Medi

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Our recent study showed that bradykinin increases cell cycling progression and migration of human cardiac c‐Kit+ progenitor cells by activating pAkt and pERK1/2 signals. This study investigated whether bradykinin‐mediated Ca2+ signalling participates in regulating cellular functions in cultured human cardiac c‐Kit+ progenitor cells using laser scanning confocal microscopy and biochemical approaches. It was found that bradykinin increased cytosolic free Ca2+ (Canormali2+) by triggering a transient Ca2+ release from ER IP3Rs followed by sustained Ca2+ influx through store‐operated Ca2+ entry (SOCE) channel. Blockade of B2 receptor with HOE140 or IP3Rs with araguspongin B or silencing IP3R3 with siRNA abolished both Ca2+ release and Ca2+ influx. It is interesting to note that the bradykinin‐induced cell cycle progression and migration were not observed in cells with siRNA‐silenced IP3R3 or the SOCE component TRPC1, Orai1 or STIM1. Also the bradykinin‐induced increase in pAkt and pERK1/2 as well as cyclin D1 was reduced in these cells. These results demonstrate for the first time that bradykinin‐mediated increase in free Canormali2+ via ER‐IP3R3 Ca2+ release followed by Ca2+ influx through SOCE channel plays a crucial role in regulating cell growth and migration via activating pAkt, pERK1/2 and cyclin D1 in human cardiac c‐Kit+ progenitor cells.

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“…[27][28][29] In this study, we found that mechanical stretch induced by nanoparticles, in this case QDs, elevated [Ca 2+ ] i in the Calu-3 epithelial cell layer and that this elevation was suppressed ] i signals in both excitable and nonexcitable cells is the family of storeoperated Ca 2+ channels, which responds to the reduction of ER intraluminal Ca 2+ entry. 30 The SOCE has been shown to play an important role in the ciliary beating and ion transport of airway epithelial cells. 11,26 Our study indicated that SOCE inhibitor BTP2 could inhibit the [Ca 2+ ] i increase in response to QD deposition in Calu-3 layer.…”

Section: Discussionmentioning

confidence: 99%

Quantum dots modulate intracellular Ca<sup>2+</sup> level in lung epithelial cells

Yin

Fontana

Solandt

et al. 2017

IJN

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While adverse effects of nanoparticles on lung health have previously been proposed, few studies have addressed the direct effects of nanoparticle exposure on the airway epithelium. In this work, we examine the response of the pulmonary airway to nanoparticles by measuring intracellular Ca 2+ concentration ([Ca 2+ ] i ) in the Calu-3 epithelial layer stimulated by 3-mercaptopropionic-acid (3MPA) coated CdSe-CdS/ZnS core-multishell quantum dots (QDs). Simultaneous transient transepithelial electrical resistance (TEER) decrease and global [Ca 2+ ] i increase in Calu-3 epithelial layer, accompanied by cell displacements, contraction, and expansion, were observed under QD deposition. This suggests that a QD-induced global [Ca 2+ ] i increase in the Calu-3 epithelial layer caused the transient TEER decrease. The [Ca 2+ ] i increase was marked and rapid in the apical region, while [Ca 2+ ] i decreased in the basolateral region of the epithelial layer. TEER transient response and extracellular Ca 2+ entry induced by QD deposition were completely inhibited in cells treated with stretched-activated (SA) inhibitor GdCl 3 and store-operated calcium entry (SOCE) inhibitor BTP2 and in cells immersed in Ca 2+ -free medium. The voltage-gated calcium channel (VGCC) inhibitor nifedipine decreased, stabilized, and suppressed the TEER response, but did not affect the [Ca 2+ ] i increase, due to QD deposition. This demonstrates that the Ca 2+ influx activated by QDs’ mechanical stretch occurs through activation of both SA and SOCE channels. QD-induced [Ca 2+ ] i increase occurred in the Calu-3 epithelial layer after culturing for 15 days, while significant TEER drop only occurred after 23 days. This work provides a new perspective from which to study direct interactions between airway epithelium and nanoparticles and may help to reveal the pathologies of pulmonary disease.

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Store-Operated Calcium Channels

Cited by 1,005 publications

References 479 publications

The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca²⁺-dependent inactivation

The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca²⁺-dependent inactivation

Bradykinin‐mediated Ca²⁺ signalling regulates cell growth and mobility in human cardiac c‐Kit⁺ progenitor cells

Quantum dots modulate intracellular Ca<sup>2+</sup> level in lung epithelial cells

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Store-Operated Calcium Channels

Cited by 1,005 publications

References 479 publications

The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca2+-dependent inactivation

The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca2+-dependent inactivation

Bradykinin‐mediated Ca2+ signalling regulates cell growth and mobility in human cardiac c‐Kit+ progenitor cells

Quantum dots modulate intracellular Ca<sup>2+</sup> level in lung epithelial cells

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The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca²⁺-dependent inactivation

The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca²⁺-dependent inactivation

Bradykinin‐mediated Ca²⁺ signalling regulates cell growth and mobility in human cardiac c‐Kit⁺ progenitor cells