ArticleThe Journal of biological chemistry2012
Bidirectional coupling between ryanodine receptors and Ca2+ release-activated Ca2+ (CRAC) channel machinery sustains store-operated Ca2+ entry in human T lymphocytes.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Guardians of T-Cell CaCells · 2026Review
- Dantrolene normalizes heightened CaCell calcium · 2025Article
- SERCA Modulators Reveal Distinct Signaling and Functional Roles of T Lymphocyte CaInternational journal of molecular sciences · 2024Article
- Orai, RyR, and IPCommunications biology · 2023Article
- Role of ryanodine receptor 2 and FK506-binding protein 12.6 dissociation in pulmonary hypertension.The Journal of general physiology · 2023Article
- Electrical signals in the ER are cell type and stimulus specific with extreme spatial compartmentalization in neurons.Cell reports · 2023Article
- Mitochondrial dysfunctions in T cells: focus on inflammatory bowel disease.Frontiers in immunology · 2023Review
- Store-Operated CaCancers · 2022Article
- Ryanodine receptor and immune-related molecules in diabetic cardiomyopathy.ESC heart failure · 2021Review
- T lymphocytes from malignant hyperthermia-susceptible mice display aberrations in intracellular calcium signaling and mitochondrial function.Cell calcium · 2021Article
- Regulatory Network Analysis of Mutated Genes Based on Multi-Omics Data Reveals the Exclusive Features in Tumor Immune Microenvironment Between Left-Sided and Right-Sided Colon Cancer.Frontiers in oncology · 2021Article
- Modulation of Ryanodine Receptors Activity Alters the Course of Experimental Autoimmune Encephalomyelitis in Mice.Frontiers in physiology · 2021Article
- Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects.Pharmaceuticals (Basel, Switzerland) · 2020Review
- TRIC-A shapes oscillatory Ca2+ signals by interaction with STIM1/Orai1 complexes.PLoS biology · 2020Article
- Review
- Dysregulation of Neuronal Calcium Signaling via Store-Operated Channels in Huntington's Disease.Frontiers in cell and developmental biology · 2020Review
- Calcium signalling in T cells.Nature reviews. Immunology · 2019Review
- Conformation of ryanodine receptor-2 gates store-operated calcium entry in rat pulmonary arterial myocytes.Cardiovascular research · 2016Article
- The functional contribution of calcium ion flux heterogeneity in T cells.Immunology and cell biology · 2015Review
- Signature Channels of Excitability no More: L-Type Channels in Immune Cells.Frontiers in immunology · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression and functional significance of ryanodine receptors (RyR) were investigated in resting and activated primary human T cells. RyR1, RyR2, and RyR3 transcripts were detected in human T cells. RyR1/2 transcript levels increased, whereas those of RyR3 decreased after T cell activation. RyR1/2 protein immunoreactivity was detected in activated but not in resting T cells. The RyR agonist caffeine evoked Ca(2+) release from the intracellular store in activated T cells but not in resting T cells, indicating that RyR are functionally up-regulated in activated T cells compared with resting T cells. In the presence of store-operated Ca(2+) entry (SOCE) via plasmalemmal Ca(2+) release-activated Ca(2+) (CRAC) channels, RyR blockers reduced the Ca(2+) leak from the endoplasmic reticulum (ER) and the magnitude of SOCE, suggesting that a positive feedback relationship exists between RyR and CRAC channels. Overexpression of fluorescently tagged RyR2 and stromal interaction molecule 1 (STIM1), an ER Ca(2+) sensor gating CRAC channels, in HEK293 cells revealed that RyR are co-localized with STIM1 in the puncta formed after store depletion. These data indicate that in primary human T cells, the RyR are coupled to CRAC channel machinery such that SOCE activates RyR via a Ca(2+)-induced Ca(2+) release mechanism, which in turn reduces the Ca(2+) concentration within the ER lumen in the vicinity of STIM1, thus facilitating SOCE by reducing store-dependent CRAC channel inactivation. Treatment with RyR blockers suppressed activated T cell expansion, demonstrating the functional importance of RyR in T cells.
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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.