Over-expression of Orai1 mediates cell proliferation and associates with poor prognosis in human non-small cell lung carcinoma.

Zhengyu Zhan,

Lu-Xing Zhong,

Feng Miao

et al.

PubMed, Journal Year: 2015, Volume and Issue: 8(5), P. 5080 - 8

Published: Jan. 1, 2015

Orai1 and STIM1 mediate calcium release-activated current (CRAC) which is the best characterized store-operated involving in a wide range of cell progresses, such as proliferation, metastasis, apoptosis. has been studied carcinogenic biomarker some cancers esophageal cancer. However, its function clinical significance non-small lung cancer (NSCLC) have not well studied. The present study was aimed at discussing relationship between malignant behavior with significance. We used quantitative real-time-PCR Western blot to detect expression NSCLC lines fresh tissues. Immunohistochemistry were performed test location paraffin sections. found that markedly overexpressed both data also revealed overexpression 42.4% tissues, compared corresponding adjacent nontumorous Furthermore, patients high survived shorter than those low expression. In addition, when knockdown by RNAi technic, we PI3k/AKT/ERK pathway inhibited may indicated could influence proliferation. Taken together, our demonstrated remarkably be served potential prognostic marker for this deadly disease.

Language: Английский

Store-Operated Calcium Channels DOI
Murali Prakriya, Richard S. Lewis

Physiological Reviews, Journal Year: 2015, Volume and Issue: 95(4), P. 1383 - 1436

Published: Sept. 24, 2015

Store-operated calcium channels (SOCs) are a major pathway for signaling in virtually all metozoan cells and serve wide variety of functions ranging from gene expression, motility, secretion to tissue organ development the immune response. SOCs activated by depletion Ca 2+ endoplasmic reticulum (ER), triggered physiologically through stimulation diverse set surface receptors. Over 15 years after first characterization electrophysiology, identification STIM proteins as ER sensors Orai store-operated has enabled rapid progress understanding unique mechanism store-operate entry (SOCE). Depletion causes accumulate at ER-plasma membrane (PM) junctions where it traps activates diffusing closely apposed PM. Mutagenesis studies combined with recent structural insights about now beginning reveal molecular underpinnings these choreographic events. This review describes experimental advances underlying our current how is coupled activation SOCs. Particular emphasis placed on mechanisms activation, channel properties, modulation function, pharmacological inhibitors SOCE, physiology disease.

Language: Английский

Citations

1086
Regulation of neurogenesis by calcium signaling DOI
Anna B. Toth,

Andrew Shum,

Murali Prakriya

et al.

Cell Calcium, Journal Year: 2016, Volume and Issue: 59(2-3), P. 124 - 134

Published: March 1, 2016

Language: Английский

Citations

142
Distinct Spatial Ca2+ Signatures Selectively Activate Different NFAT Transcription Factor Isoforms DOI Creative Commons

Pulak Kar,

Anant B. Parekh

Molecular Cell, Journal Year: 2015, Volume and Issue: 58(2), P. 232 - 243

Published: April 1, 2015

Protein isoforms are widely expressed in biological systems. How that co-exist within the same sub-cellular domain differentially activated remains unclear. Here, we compare regulatory mechanism of two closely related transcription factor isoforms, NFAT1 and NFAT4, migrate from cytoplasm to nucleus following increase intracellular Ca2+ accompanies opening store-operated Orai1/CRAC channels. We demonstrate has a private line communication with Orai1, activating response microdomains near open By contrast, NFAT4 stimulation requires both local entry nuclear rise. mapped differences location amino acids SP-3 motif NFAT domain. The different dependencies enable agonists recruit isoform combinations as stimulus strength increases. Our study uncovers whereby co-existing cytoplasmic by distinct signals.

Language: Английский

Citations

123
STIM and ORAI proteins in the nervous system DOI Open Access
Robert Kraft

Channels, Journal Year: 2015, Volume and Issue: 9(5), P. 245 - 252

Published: July 28, 2015

Stromal interaction molecules (STIM) 1 and 2 are sensors of the calcium concentration in endoplasmic reticulum. Depletion reticulum stores activates STIM proteins which, turn, bind open channels plasma membrane formed by ORAI1, ORAI2, ORAI3. The resulting store-operated entry (SOCE), mostly controlled principal components STIM1 has been particularly characterized immune cells. In nervous system, all ORAI homologs expressed. This review summarizes current knowledge on distribution function central neurons glial cells, i.e. astrocytes microglia. STIM2 is required for SOCE hippocampal synapses cortical neurons, whereas controls store replenishment cerebellar Purkinje neurons. microglia, STIM1, STIM2, ORAI1 regulate migration phagocytosis. isoforms ORAI2 ORAI3 candidates astrocytes, respectively. Due to role neuronal homeostasis, dysfunction may have consequences development neurodegenerative disorders, such as Alzheimer's disease.

Language: Английский

Citations

111
Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis DOI Creative Commons
Saul Soberanes, Alexander V. Misharin, Amit Jairaman

et al.

Cell Metabolism, Journal Year: 2018, Volume and Issue: 29(2), P. 335 - 347.e5

Published: Oct. 11, 2018

Language: Английский

Citations

103
Alternative splicing converts STIM2 from an activator to an inhibitor of store-operated calcium channels DOI Creative Commons

Anshul Rana,

Michelle Yen,

Amir Masoud Sadaghiani

et al.

The Journal of Cell Biology, Journal Year: 2015, Volume and Issue: 209(5), P. 653 - 670

Published: June 1, 2015

Store-operated calcium entry (SOCE) regulates a wide variety of essential cellular functions. SOCE is mediated by STIM1 and STIM2, which sense depletion ER Ca2+ stores activate Orai channels in the plasma membrane. Although amplitude dynamics are considered important determinants Ca2+-dependent responses, underlying modulatory mechanisms unclear. In this paper, we identify STIM2β, highly conserved alternatively spliced isoform which, contrast to all known STIM isoforms, potent inhibitor SOCE. STIM2β does not itself strongly bind Orai1, it recruited Orai1 forming heterodimers with other isoforms. Analysis mutants Orai1-STIM2β chimeras suggested that actively inhibits through sequence-specific allosteric interaction Orai1. Our results reveal previously unrecognized functional flexibility protein family alternative splicing creates negative positive regulators shape signals.

Language: Английский

Citations

101
Epithelial Sodium Channel Regulates Adult Neural Stem Cell Proliferation in a Flow-Dependent Manner DOI Creative Commons
David Petřík, Michael H. Myoga, Sofia Grade

et al.

Cell stem cell, Journal Year: 2018, Volume and Issue: 22(6), P. 865 - 878.e8

Published: May 17, 2018

Language: Английский

Citations

95
SOCE in neurons: Signaling or just refilling? DOI Creative Commons
Łukasz Majewski, Jacek Kuźnicki

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2015, Volume and Issue: 1853(9), P. 1940 - 1952

Published: Jan. 31, 2015

In this review we describe the present knowledge about store operated Ca2 + entry (SOCE) in neurons and proteins involved process: STIM, as well Orai TRP channels. We address issue of whether SOCE is used only to refill ER or that enters neuronal cell during also performs signaling functions. collected data indicating its components participate important processes neurons. This has implications for identifying new drug targets treatment brain diseases. Evidence indicates neurodegenerative diseases homeostasis become dysregulated. Thus, different strategies might be identified potential these article part a Special Issue entitled: 13th European symposium on calcium.

Language: Английский

Citations

93
Astrocyte reactivity and inflammation-induced depression-like behaviors are regulated by Orai1 calcium channels DOI Creative Commons
Michaela Novakovic,

Kirill S. Korshunov,

Rogan A. Grant

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 7, 2023

Abstract Astrocytes contribute to brain inflammation in neurological disorders but the molecular mechanisms controlling astrocyte reactivity and their relationship neuroinflammatory endpoints are complex poorly understood. In this study, we assessed role of calcium channel, Orai1, for inflammation-evoked depression behaviors mice. Transcriptomics metabolomics analysis indicated that deletion Orai1 astrocytes downregulates genes immunity, metabolism, cell cycle pathways, reduces cellular metabolites ATP production. Systemic by peripheral lipopolysaccharide (LPS) increases hippocampal inflammatory markers WT not knockout Loss also blunts inflammation-induced Ca 2+ signaling inhibitory neurotransmission hippocampus. line with these changes, mice showed amelioration LPS-evoked depression-like including anhedonia helplessness. These findings identify as an important hub astrocyte-mediated is commonly observed many disorders.

Language: Английский

Citations

37
Regulation of neuropathic pain by microglial Orai1 channels DOI Creative Commons
Shogo Tsujikawa, Kaitlyn E. DeMeulenaere, Maria Virginia Centeno

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(4)

Published: Jan. 27, 2023

Microglia are important mediators of neuroinflammation, which underlies neuropathic pain. However, the molecular checkpoints controlling microglial reactivity not well-understood. Here, we investigated role Orai1 channels for microglia-mediated neuroinflammation following nerve injury and find that deletion in microglia attenuates Ca 2+ signaling production inflammatory cytokines by proalgesic agonists. Conditional attenuated proliferation dorsal horn, spinal cytokine levels, potentiation excitatory neurotransmission peripheral injury. These cellular effects were accompanied mitigation pain hyperalgesia knockout mice. A small-molecule inhibitor, CM4620, similarly mitigated allodynia male Unexpectedly, these protective seen female mice, revealing sexual dimorphism regulation hyperalgesia. Together, findings indicate key regulators sexually dimorphic

Language: Английский

Citations

24