ArticleMolecular and cellular biology2013
Mechanisms of STIM1 activation of store-independent leukotriene C4-regulated Ca2+ channels.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Engineering of genetically encoded programmable calcium channel inhibitory binders.Nature communications · 2026Article
- Integrin activation by two independently regulated calcium-mediated pathways is required for neutrophil recruitment.Cell communication and signaling : CCS · 2026Article
- Loss of STIM2, but not of STIM1, drives colorectal cancer metastasis through metabolic reprogramming and the ATF4 ER stress pathway.Science signaling · 2025Article
- ORAI CaBiomolecules · 2024Review
- Too much of a good thing: The case of SOCE in cellular apoptosis.Cell calcium · 2023Review
- Article
- ORAI3 is dispensable for store-operated Ca2+ entry and immune responses by lymphocytes and macrophages.The Journal of general physiology · 2022Article
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
- 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
- Omnitemporal choreographies of all five STIM/Orai and IPCell reports · 2021Article
- The anatomy ofCurrent opinion in physiology · 2020Article
- STIM1-mediated calcium influx controls antifungal immunity and the metabolic function of non-pathogenic Th17 cells.EMBO molecular medicine · 2020Article
- The native ORAI channel trio underlies the diversity of CaNature communications · 2020Article
- ORAI channels in cellular remodeling of cardiorespiratory disease.Cell calcium · 2019Review
- Cross-talk between N-terminal and C-terminal domains in stromal interaction molecule 2 (STIM2) determines enhanced STIM2 sensitivity.The Journal of biological chemistry · 2019Article
- Calcium signalling in T cells.Nature reviews. Immunology · 2019Review
- STIM1 thermosensitivity defines the optimal preference temperature for warm sensation in mice.Cell research · 2019Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
We recently showed, in primary vascular smooth muscle cells (VSMCs), that the platelet-derived growth factor activates canonical store-operated Ca(2+) entry and Ca(2+) release-activated Ca(2+) currents encoded by Orai1 and STIM1 genes. However, thrombin activates store-independent Ca(2+) selective channels contributed by both Orai3 and Orai1. These store-independent Orai3/Orai1 channels are gated by cytosolic leukotriene C4 (LTC4) and require STIM1 downstream LTC4 action. However, the source of LTC4 and the signaling mechanisms of STIM1 in the activation of this LTC4-regulated Ca(2+) (LRC) channel are unknown. Here, we show that upon thrombin stimulation, LTC4 is produced through the sequential activities of phospholipase C, diacylglycerol lipase, 5-lipo-oxygenease, and leukotriene C4 synthase. We show that the endoplasmic reticulum-resident STIM1 is necessary and sufficient for LRC channel activation by thrombin. STIM1 does not form sustained puncta and does not colocalize with Orai1 either under basal conditions or in response to thrombin. However, STIM1 is precoupled to Orai3 and Orai3/Orai1 channels under basal conditions as shown using Forster resonance energy transfer (FRET) imaging. The second coiled-coil domain of STIM1 is required for coupling to either Orai3 or Orai3/Orai1 channels and for LRC channel activation. We conclude that STIM1 employs distinct mechanisms in the activation of store-dependent and store-independent Ca(2+) entry pathways.
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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.