ArticleMolecular pharmacology2012
The Ca(2+) sensor stromal interaction molecule 1 (STIM1) is necessary and sufficient for the store-operated Ca(2+) entry function of transient receptor potential canonical (TRPC) 1 and 4 channels in endothelial cells.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 113 citations in OpenAlex.
- Transient receptor potential canonical (TRPC) channels in diabetes and associated complications.Channels (Austin, Tex.) · 2026Review
- Ginsenoside Compound K Differentially Regulates Neuronal and Astrocytic CaPharmaceuticals (Basel, Switzerland) · 2026Article
- TRPC channels contribute to endothelial dysfunction in pulmonary arterial hypertension.Respiratory research · 2025Article
- The Molecular Heterogeneity of Store-Operated CaInternational journal of molecular sciences · 2023Review
- The transient receptor potential channels in rheumatoid arthritis: Need to pay more attention.Frontiers in immunology · 2023Review
- An ex vivo perfused ventilated murine lung model suggests lack of acute pulmonary toxicity of the potential novel anticancer agent (-)-englerin A.Archives of toxicology · 2022Article
- Role of Ion Channel Remodeling in Endothelial Dysfunction Induced by Pulmonary Arterial Hypertension.Biomolecules · 2022Review
- Role of store-operated Ca2+ entry in cardiovascular disease.Cell communication and signaling : CCS · 2022Review
- Calcium-Permeable Channels in Tumor Vascularization: Peculiar Sensors of Microenvironmental Chemical and Physical Cues.Reviews of physiology, biochemistry and pharmacology · 2022Review
- TRP Channels as Molecular Targets to Relieve Endocrine-Related Diseases.Frontiers in molecular biosciences · 2022Review
- Endothelial Ion Channels and Cell-Cell Communication in the Microcirculation.Frontiers in physiology · 2022Review
- Role of Store-Operated CaBiomolecules · 2021Review
- Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum.The Journal of cell biology · 2021Article
- TRPC channel-derived calcium fluxes differentially regulate ATP and flow-induced activation of eNOS.Nitric oxide : biology and chemistry · 2021Article
- Electrophysiological Properties of Endogenous Single CaInternational journal of molecular sciences · 2021Article
- Proteins Interacting with STIM1 and Store-Operated CaProgress in molecular and subcellular biology · 2021Review
- Store-Operated Calcium Channels as Drug Target in Gastroesophageal Cancers.Frontiers in pharmacology · 2021Review
- Vascular Dysfunction in Diabetes and Obesity: Focus on TRP Channels.Frontiers in physiology · 2021Review
- Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular CaCellular and molecular life sciences : CMLS · 2020Article
- TRPC channels: Structure, function, regulation and recent advances in small molecular probes.Pharmacology & therapeutics · 2020Review
6 more citing papers are in PubMed but not listed here.
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8 authors at 2 institutions in 1 country.
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Abstract
We addressed the requirement for stromal interaction molecule 1 (STIM1), the endoplasmic reticulum (ER) Ca(2+)-sensor, and Orai1, a Ca(2+) selective channel, in regulating Ca(2+) entry through the store-operated channels mouse transient receptor potential canonical (TRPC) 4 or human TRPC1. Studies were made using murine and human lung endothelial cells (ECs) challenged with thrombin known to induce Ca(2+) entry via TRPC1/4. Deletion or knockdown of TRPC4 abolished Ca(2+) entry secondary to depletion of ER Ca(2+) stores, preventing the disruption of the endothelial barrier. Knockdown of STIM1 (but not of Orai1or Orai3) or expression of the dominant-negative STIM1(K684E-K685E) mutant in ECs also suppressed Ca(2+) entry secondary to store depletion. Ectopic expression of WT-STIM1 or WT-Orai1 in TRPC4(-/-)-ECs failed to rescue Ca(2+) entry; however, WT-TRPC4 expression in TRPC4(-/-)-ECs restored Ca(2+) entry indicating the requirement for TRPC4 in mediating store-operated Ca(2+) entry. Moreover, expression of the dominant-negative Orai1(R91W) mutant or Orai3(E81W) mutant in WT-ECs failed to prevent thrombin-induced Ca(2+) entry. In contrast, expression of the dominant-negative TRPC4(EE647-648KK) mutant in WT-ECs markedly reduced thrombin-induced Ca(2+) entry. In ECs expressing YFP-STIM1, ER-store Ca(2+) depletion induced formation of fluorescent membrane puncta in WT but not in TRPC4(-/-) cells, indicating that mobilization of STIM1 and engagement of its Ca(2+) sensing function required TRPC4 expression. Coimmunoprecipitation studies showed coupling of TRPC1 and TRPC4 with STIM1 on depletion of ER Ca(2+) stores. Thus, TRPC1 and TRPC4 can interact with STIM1 to form functional store-operated Ca(2+)-entry channels, which are essential for mediating Ca(2+) entry-dependent disruption of the endothelial barrier.
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