A calcium-accumulating region, CAR, in the channel Orai1 enhances Ca 2+ permeation and SOCE-induced gene transcription DOI
Irene Frischauf, Vasilina Zayats,

Michael Deix

и другие.

Science Signaling, Год журнала: 2015, Номер 8(408)

Опубликована: Дек. 22, 2015

The Ca(2+) release-activated channel mediates influx in a plethora of cell types, thereby controlling diverse cellular functions. complex is composed stromal interaction molecule 1 (STIM1), an endoplasmic reticulum Ca(2+)-sensing protein, and Orai1, plasma membrane channel. Channels STIM1 Orai1 mediate even at low extracellular concentrations. We investigated whether the activity adapted to different environmental used homology modeling molecular dynamics simulations predict presence Ca(2+)-accumulating region (CAR) pore entrance Orai1. Furthermore, proteins with mutations CAR, along live-cell experiments, or electrophysiological recordings transient, electrostatic loop3 interacting loop1 (the site CAR) determined that CAR enhanced permeation most efficiently external Consistent these results, cells expressing mutants exhibited impaired gene expression stimulated by Ca(2+)-activated transcription factor nuclear activated T (NFAT). propose architecture close proximity selectivity filter, which enables Ca(2+)-selective ion permeation, enhances local concentration maintain Ca(2+)-dependent regulation environments relatively Ca(2+)concentrations.

Язык: Английский

ORAI Calcium Channels DOI Open Access
Mohamed Trebak, James W. Putney

Physiology, Год журнала: 2017, Номер 32(4), С. 332 - 342

Опубликована: Июнь 15, 2017

In this review article, we discuss the different gene products and translational variants of ORAI proteins their contribution to makeup native calcium-conducting channels with distinct compositions modes activation. We also regulation these calcium impact on downstream cellular signaling controlling important physiological functions.

Язык: Английский

Процитировано

82
A calcium optimum for cytotoxic T lymphocyte and natural killer cell cytotoxicity DOI Open Access
Xiao Qin Zhou, Kim S. Friedmann,

Hélène Lyrmann

и другие.

The Journal of Physiology, Год журнала: 2018, Номер 596(14), С. 2681 - 2698

Опубликована: Янв. 25, 2018

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are required to eliminate cancer cells. We analysed the Ca2+ dependence of CTL NK cell cytotoxicity found that in particular CTLs have a very low optimum [Ca2+ ]i (between 122 334 nm) ]o 23 625 μm) for efficient elimination, well below blood plasma levels. As predicted from these results, partial down-regulation channel Orai1 paradoxically increases perforin-dependent killing. Lytic granule release at immune synapse between has compatible with this killing, whereas migration is slightly higher proliferation monotonously increasing . propose inhibition signals by specific blockers submaximal concentrations could contribute tumour elimination.Cytotoxic protect human body against cancer. key metabolic factor lymphocyte function homeostasis. bell-shaped an elimination rather (23-625 (122-334 nm). This finding predicts should increase (rather than decrease) μm. tested hypothesis indeed siRNA efficiency two mechanisms may account killing: (1) velocity persistence moderate 500 1000 μm CTLs, (2) lytic increased 146 compared 3 or 800 μm, It been demonstrated many types Orai1-dependent enhance proliferation. decrease activity selective microenvironment efficiently reduce growth simultaneously decreasing

Язык: Английский

Процитировано

77
Calcium signalling and breast cancer DOI
Choon Leng So, Jodi M. Saunus, Sarah J. Roberts‐Thomson

и другие.

Seminars in Cell and Developmental Biology, Год журнала: 2018, Номер 94, С. 74 - 83

Опубликована: Ноя. 16, 2018

Язык: Английский

Процитировано

76
Transmembrane helix connectivity in Orai1 controls two gates for calcium-dependent transcription DOI Open Access
Irene Frischauf, Monika Litviňuková, Romana Schober

и другие.

Science Signaling, Год журнала: 2017, Номер 10(507)

Опубликована: Ноя. 28, 2017

Characterization of disease-associated Orai1 mutants reveals the multistep gating mechanism for CRAC channel.

Язык: Английский

Процитировано

74
Spatial and Temporal Aspects of Signaling by G-Protein–Coupled Receptors DOI Open Access
Martin J. Lohse, Klaus Peter Hofmann

Molecular Pharmacology, Год журнала: 2015, Номер 88(3), С. 572 - 578

Опубликована: Июль 16, 2015

Signaling by G-protein-coupled receptors is often considered a uniform process, whereby homogeneously activated proportion of randomly distributed are under equilibrium conditions and produce homogeneous, steady-state intracellular signals. While this may be the case in some biologic systems, example rhodopsin with its strictly local single-quantum mode function shows that homogeneity space time cannot general property systems. Recent work has now revealed many other systems where such simplicity does not prevail. Instead, plethora mechanisms allows much more complex patterns receptor activation signaling: different protein-protein interaction; temporal changes nonequilibrium conditions; localized activation; second messenger generation degradation-all which shape receptor-generated signals permit creation multiple signal types. Here, we review evidence for pleiotropic signaling time.

Язык: Английский

Процитировано

72
Optogenetic Control of Calcium Oscillation Waveform Defines NFAT as an Integrator of Calcium Load DOI Creative Commons
Pimkhuan Hannanta‐anan,

Brian Y. Chow

Cell Systems, Год журнала: 2016, Номер 2(4), С. 283 - 288

Опубликована: Апрель 1, 2016

Язык: Английский

Процитировано

72
STIM1 dimers undergo unimolecular coupling to activate Orai1 channels DOI Creative Commons
Yandong Zhou, Xizhuo Wang,

Xianming Wang

и другие.

Nature Communications, Год журнала: 2015, Номер 6(1)

Опубликована: Сен. 24, 2015

Abstract The endoplasmic reticulum (ER) Ca 2+ sensor, STIM1, becomes activated when ER-stored is depleted and translocates into ER–plasma membrane junctions where it tethers activates Orai1 entry channels. dimeric STIM1 protein contains a small STIM-Orai-activating region (SOAR)—the minimal sequence sufficient to activate Since SOAR itself dimer, we constructed concatemer–dimers introduced mutations at F394, which critical for coupling activation. F394H mutation in both monomers completely blocks dimer function, but only one of the has no effect on binding or This reveals an unexpected unimolecular between argues against recent evidence suggesting interaction two adjacent channel subunits. model predicts that dimers may be involved crosslinking channels with implications kinetics localization opening.

Язык: Английский

Процитировано

71
STIM2 Induces Activated Conformation of STIM1 to Control Orai1 Function in ER-PM Junctions DOI Creative Commons

Krishna Prasad Subedi,

Hwei Ling Ong, Ga‐Yeon Son

и другие.

Cell Reports, Год журнала: 2018, Номер 23(2), С. 522 - 534

Опубликована: Апрель 1, 2018

Ca2+ entry mediated by the calcium channel, Orai1, provides critical signals that regulate cell function. The ER-Ca2+ sensor protein, STIM1, recruits and strongly activates Orai1 within ER-PM junctions. STIM2 is a poor activator of its physiological role not well understood. Herein, we report crucial function for in inducing activated conformation STIM1. By using conformational sensors together with protein interaction functional studies, show constitutively localized junctions store replete cells. Importantly, traps STIM1 triggers remodeling C terminus, causing STIM1/Orai1 coupling enhancement cells relatively high ER-[Ca2+]. increase controls Ca2+-dependent transcription factor, NFAT, activation at low [agonist]. Our findings reveal modulates to tune fidelity receptor-evoked signaling response

Язык: Английский

Процитировано

71
Acetylcholine induces intracellular Ca2+ oscillations and nitric oxide release in mouse brain endothelial cells DOI
Estella Zuccolo, Dmitry Lim, Dlzar A. Kheder

и другие.

Cell Calcium, Год журнала: 2017, Номер 66, С. 33 - 47

Опубликована: Июнь 12, 2017

Язык: Английский

Процитировано

69
Control of NFAT Isoform Activation and NFAT-Dependent Gene Expression through Two Coincident and Spatially Segregated Intracellular Ca 2+ Signals DOI Creative Commons

Pulak Kar,

Gary R. Mirams, Helen Christian

и другие.

Molecular Cell, Год журнала: 2016, Номер 64(4), С. 746 - 759

Опубликована: Ноя. 1, 2016

Excitation-transcription coupling, linking stimulation at the cell surface to changes in nuclear gene expression, is conserved throughout eukaryotes. How closely related coexpressed transcription factors are differentially activated remains unclear. Here, we show that two Ca2+-dependent factor isoforms, NFAT1 and NFAT4, require distinct sub-cellular InsP3 Ca2+ signals for physiologically sustained activation. stimulated by sub-plasmalemmal microdomains, whereas NFAT4 additionally requires mobilization from inner envelope receptors. rephosphorylated (deactivated) more slowly than both cytoplasm nucleus, enabling a prolonged activation phase. Oscillations cytoplasmic Ca2+, long considered physiological form of signaling, play no role activating either NFAT protein. Instead, effective tightly linked oscillations Ca2+. Our results how expression can be controlled coincident yet geographically signals, generated freely diffusible message.

Язык: Английский

Процитировано

67