ArticleThe Journal of physiology2008
Both Orai1 and Orai3 are essential components of the arachidonate-regulated Ca2+-selective (ARC) channels.
Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
92 citing papers in PubMed, 157 citations in OpenAlex.
- Research progress on the role and mechanism of STIM and Orai protein-mediated store-operated calcium entry in cardiovascular diseases.Channels (Austin, Tex.) · 2026Review
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Differential functional role of Orai1 variants in constitutive CaThe Journal of biological chemistry · 2024Article
- Calcium channel signalling at neuronal endoplasmic reticulum-plasma membrane junctions.Biochemical Society transactions · 2024Review
- Pathophysiological Roles of Ion Channels in Epidermal Cells, Immune Cells, and Sensory Neurons in Psoriasis.International journal of molecular sciences · 2024Review
- p38 MAPK activation and STIM1-Orai3 association mediate TRPC6 externalization.American journal of physiology. Cell physiology · 2023Article
- Too much of a good thing: The case of SOCE in cellular apoptosis.Cell calcium · 2023Review
- Regulatory mechanisms controlling store-operated calcium entry.Frontiers in physiology · 2023Review
- Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β.International journal of molecular sciences · 2022Review
- ORAI3 is dispensable for store-operated Ca2+ entry and immune responses by lymphocytes and macrophages.The Journal of general physiology · 2022Article
- ORAI1-Regulated Gene Expression in Breast Cancer Cells: Roles for STIM1 Binding, Calcium Influx and Transcription Factor Translocation.International journal of molecular sciences · 2022Article
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
- Role of Store-Operated CaBiomolecules · 2021Review
- Orai3 Regulates Pancreatic Cancer Metastasis by Encoding a Functional Store Operated Calcium Entry Channel.Cancers · 2021Article
- Role of Orai3 in the Pathophysiology of Cancer.International journal of molecular sciences · 2021Review
- Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology.International journal of molecular sciences · 2021Review
- The Orai1-AC8 Interplay: How Breast Cancer Cells Escape from Orai1 Channel Inactivation.Cells · 2021Review
- Arachidonic acid-regulated calcium signaling in T cells from patients with rheumatoid arthritis promotes synovial inflammation.Nature communications · 2021Article
- Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and CaReviews of physiology, biochemistry and pharmacology · 2021Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Agonist-activated Ca(2+) signals in non-excitable cells are profoundly influenced by calcium entry via both store-operated and store-independent conductances. Recent studies have demonstrated that STIM1 plays a key role in the activation of store-operated conductances including the Ca(2+)-release-activated Ca(2+) (CRAC) channels, and that Orai1 comprises the pore-forming component of these channels. We recently demonstrated that STIM1 also regulates the activity of the store-independent, arachidonic acid-regulated Ca(2+) (ARC) channels, but does so in a manner entirely distinct from its regulation of the CRAC channels. This shared ability to be regulated by STIM1, together with their similar biophysical properties, suggested that these two distinct conductances may be molecularly related. Here, we report that whilst the levels of Orai1 alone determine the magnitude of the CRAC channel currents, both Orai1 and the closely related Orai3 are critical for the corresponding currents through ARC channels. Thus, in cells stably expressing STIM1, overexpression of Orai1 increases both CRAC and ARC channel currents. Whilst similar overexpression of Orai3 alone has no effect, ARC channel currents are specifically increased by expression of Orai3 in cells stably expressing Orai1. Moreover, expression of a dominant-negative mutant Orai3, either alone or in cells expressing wild-type Orai1, profoundly and specifically reduces currents through the ARC channels without affecting those through the CRAC channels, and siRNA-mediated knockdown of either Orai1 or Orai3 markedly inhibits ARC channel currents. Importantly, our data also show that the precise effects observed critically depend on which of the three proteins necessary for effective ARC channel activity (STIM1, Orai1 and Orai3) are rate limiting under the specific conditions employed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.