ArticleProceedings of the National Academy of Sciences of the United States of America2007
Orai proteins interact with TRPC channels and confer responsiveness to store depletion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
150 citing papers in PubMed, 1 synthesis or guideline pooled it, 295 citations in OpenAlex.
- TRP Channels Interactome as a Novel Therapeutic Target in Breast Cancer.Frontiers in oncology · 2021Pooled it
- Urotensin II Receptor Deletion Mitigates Kidney Injury and Renal Lipid Remodeling in Mice Fed a Long-Term High-Fat Diet.FASEB bioAdvances · 2026Article
- Review
- Differential Sensitivity of TRPC- and ORAI-Mediated Calcium Entries to 1‑[2-(4-Methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl]imidazole Chloride (SKF-96365).ACS pharmacology & translational science · 2025Article
- Genetic evidence against involvement of TRPC proteins in SOCE, ROCE, and CRAC channel function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Physiological functions of calcium signaling via Orai1 in cancer.The journal of physiological sciences : JPS · 2023Review
- Store-operated CaExperimental biology and medicine (Maywood, N.J.) · 2023Review
- Orai1 is an Entotic CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 2023Review
- Reorganization and Suppression of Store-Operated Calcium Entry in Podocytes of Type 2 Diabetic Rats.International journal of molecular sciences · 2023Article
- Store-operated CaPNAS nexus · 2023Article
- The Molecular Heterogeneity of Store-Operated CaInternational journal of molecular sciences · 2023Review
- Lithium Treatment Improves Cardiac Dysfunction in Rats Deprived of Rapid Eye Movement Sleep.International journal of molecular sciences · 2022Article
- Endogenous ion channels expressed in human embryonic kidney (HEK-293) cells.Pflugers Archiv : European journal of physiology · 2022Review
- Enhanced Orai1-mediated store-operated CaThe Journal of biological chemistry · 2022Article
- Role of store-operated Ca2+ entry in cardiovascular disease.Cell communication and signaling : CCS · 2022Review
- Excitation-contraction coupling in mammalian skeletal muscle: Blending old and last-decade research.Frontiers in physiology · 2022Review
- Alteration of STIM1/Orai1-Mediated SOCE in Skeletal Muscle: Impact in Genetic Muscle Diseases and Beyond.Cells · 2021Review
- TRPC channel-derived calcium fluxes differentially regulate ATP and flow-induced activation of eNOS.Nitric oxide : biology and chemistry · 2021Article
- Endoplasmic Reticulum-Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling.International journal of molecular sciences · 2021Review
90 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The TRPC (C-type transient receptor potential) class of ion channels has been hypothesized to participate in store-operated Ca(2+) entry (SOCE). Recently, however, STIM1 and Orai1 proteins have been proposed to form SOCE channels. Whether TRPCs participate in SOCE that is dependent on or regulated by Orai has not been explored. Here we show that Orai1 physically interacts with the N and C termini of TRPC3 and TRPC6, and that in cells overexpressing either TRPC3 or TRPC6 in a store-depletion insensitive manner, these TRPCs become sensitive to store depletion upon expression of an exogenous Orai. Thus, Orai-1, -2, and -3 enhanced thapsigargin-induced calcium entry by 50-150% in cells stably overexpressing either TRPC3 or TRPC6. Orai1 expression had no significant effect on endogenous, thapsigargin-induced calcium entry in wild-type cells (HEK-293, COS1), in HEK cells expressing a thapsigargin-sensitive variant of TRPC3 (TRPC3a), or in HEK cells overexpressing another membrane protein, V1aR. Single-channel cation currents present in membrane patches of TRPC3-overexpressing cells were suppressed by expression of Orai1. We propose that Orai proteins by interacting with TRPCs act as regulatory subunits that confer STIM1-mediated store depletion sensitivity to these channels.
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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.