ArticleProceedings of the National Academy of Sciences of the United States of America2016
Junctophilin-4, a component of the endoplasmic reticulum-plasma membrane junctions, regulates Ca2+ dynamics in T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024Pooled it
- Junctophilin-2-orchestrated calcium signalosome regulates brown adipocyte thermogenesis and energy metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Junctophilin-2 Regulates Store-Operated Calcium Entry to Drive Cardiac Fibroblast Activation, Fibrotic Repair, and Angiogenesis After Myocardial Infarction.Circulation · 2025Article
- Plasma membrane curvature regulates the formation of contacts with the endoplasmic reticulum.Nature cell biology · 2024Article
- L-type CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Membrane Curvature Promotes ER-PM Contact Formation via Junctophilin-EHD Interactions.bioRxiv : the preprint server for biology · 2024Article
- Behavioral and Transcriptomic Analyses in the Indoxacarb Response of a Non-Target Damselfly Species.Insects · 2024Article
- Structure, Function, and Regulation of the Junctophilin Family.Annual review of physiology · 2024Review
- CRAC and SK Channels: Their Molecular Mechanisms Associated with Cancer Cell Development.Cancers · 2022Review
- NMR resonance assignments of the DNA binding domain of mouse Junctophilin-2.Biomolecular NMR assignments · 2022Article
- STIM Proteins and Regulation of SOCE in ER-PM Junctions.Biomolecules · 2022Review
- The role of junctophilin proteins in cellular function.Physiological reviews · 2022Review
- Structures of the junctophilin/voltage-gated calcium channel interface reveal hot spot for cardiomyopathy mutations.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The Role of Lipids in CRAC Channel Function.Biomolecules · 2022Review
- The Builders of the Junction: Roles of Junctophilin1 and Junctophilin2 in the Assembly of the Sarcoplasmic Reticulum-Plasma Membrane Junctions in Striated Muscle.Biomolecules · 2022Review
- Analysis of merged whole blood transcriptomic datasets to identify circulating molecular biomarkers of feed efficiency in growing pigs.BMC genomics · 2021Article
- Machine learning compensates fold-change method and highlights oxidative phosphorylation in the brain transcriptome of Alzheimer's disease.Scientific reports · 2021Article
- Junctophilin-4 facilitates inflammatory signalling at plasma membrane-endoplasmic reticulum junctions in sensory neurons.The Journal of physiology · 2021Article
- Keeping pain away by distancing the plasma membrane from the endoplasmic reticulum.The Journal of physiology · 2021Article
- More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Orai1 and stromal interaction molecule 1 (STIM1) mediate store-operated Ca(2+) entry (SOCE) in immune cells. STIM1, an endoplasmic reticulum (ER) Ca(2+) sensor, detects store depletion and interacts with plasma membrane (PM)-resident Orai1 channels at the ER-PM junctions. However, the molecular composition of these junctions in T cells remains poorly understood. Here, we show that junctophilin-4 (JP4), a member of junctional proteins in excitable cells, is expressed in T cells and localized at the ER-PM junctions to regulate Ca(2+) signaling. Silencing or genetic manipulation of JP4 decreased ER Ca(2+) content and SOCE in T cells, impaired activation of the nuclear factor of activated T cells (NFAT) and extracellular signaling-related kinase (ERK) signaling pathways, and diminished expression of activation markers and cytokines. Mechanistically, JP4 directly interacted with STIM1 via its cytoplasmic domain and facilitated its recruitment into the junctions. Accordingly, expression of this cytoplasmic fragment of JP4 inhibited SOCE. Furthermore, JP4 also formed a complex with junctate, a Ca(2+)-sensing ER-resident protein, previously shown to mediate STIM1 recruitment into the junctions. We propose that the junctate-JP4 complex located at the junctions cooperatively interacts with STIM1 to maintain ER Ca(2+) homeostasis and mediate SOCE in T cells.
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