ArticleThe Journal of biological chemistry2013
Mutations of the Ca2+-sensing stromal interaction molecule STIM1 regulate Ca2+ influx by altered oligomerization of STIM1 and by destabilization of the Ca2+ channel Orai1.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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
32 citing papers in PubMed, 69 citations in OpenAlex.
- 17β-Estradiol inhibits phosphorylation of stromal interaction molecule 1 (STIM1) protein: implication for store-operated calcium entry and chronic lung diseases.The Journal of biological chemistry · 2013Trial
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- A dual topology of STIM1 at the plasma membrane regulates calcium constitutive entry.Cellular and molecular life sciences : CMLS · 2026Article
- ORAI CaBiomolecules · 2024Review
- The CaScience signaling · 2023Article
- Role of STIM1 in the Regulation of Cardiac Energy Substrate Preference.International journal of molecular sciences · 2023Review
- T cell CaFrontiers in immunology · 2023Review
- Store-Operated Calcium Entry in Breast Cancer Cells Is Insensitive to Orai1 and STIM1 N-Linked Glycosylation.Cancers · 2022Article
- Control of STIM and Orai function by post-translational modifications.Cell calcium · 2022Review
- A longer isoform of Stim1 is a negative SOCE regulator but increases cAMP-modulated NFAT signaling.EMBO reports · 2022Article
- Genetic defects are common in myopathies with tubular aggregates.Annals of clinical and translational neurology · 2022Article
- Acidic Cannabinoids Suppress Proinflammatory Cytokine Release by Blocking Store-operated Calcium Entry.Function (Oxford, England) · 2022Review
- The store-operated CaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Molecular basis of allosteric Orai1 channel activation by STIM1.The Journal of physiology · 2020Review
- The Number and Position of Orai3 Units within Heteromeric Store-Operated CaInternational journal of molecular sciences · 2020Article
- The basic residues in the Orai1 channel inner pore promote opening of the outer hydrophobic gate.The Journal of general physiology · 2020Article
- Role of STIM1/ORAI1-mediated store-operated CaCell calcium · 2018Review
- The exquisitely cooperative nature of Orai1 channel activation.The Journal of general physiology · 2018Article
- Forms and functions of store-operated calcium entry mediators, STIM and Orai.Advances in biological regulation · 2018Review
- Molecular physiology and pathophysiology of stromal interaction molecules.Experimental biology and medicine (Maywood, N.J.) · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A drop of endoplasmic reticulum Ca(2+) concentration triggers its Ca(2+) ssensor protein stromal interaction molecule 1 (STIM1) to oligomerize and accumulate within endoplasmic reticulum-plasma membrane junctions where it activates Orai1 channels, providing store-operated Ca(2+) entry. To elucidate the functional significance of N-glycosylation sites of STIM1, we created different mutations of asparagine-131 and asparagine-171. STIM1 NN/DQ resulted in a strong gain of function. Patch clamp, Total Internal Reflection Fluorescent (TIRF) microscopy, and fluorescence recovery after photobleaching (FRAP) analyses revealed that expression of STIM1 DQ mutants increases the number of active Orai1 channels and the rate of STIM1 translocation to endoplasmic reticulum-plasma membrane junctions with a decrease in current latency. Surprisingly, co-expression of STIM1 DQ decreased Orai1 protein, altering the STIM1:Orai1 stoichiometry. We describe a novel mathematical tool to delineate the effects of altered STIM1 or Orai1 diffusion parameters from stoichiometrical changes. The mutant uncovers a novel mechanism whereby "superactive" STIM1 DQ leads to altered oligomerization rate constants and to degradation of Orai1 with a change in stoichiometry of activator (STIM1) to effector (Orai1) ratio leading to altered Ca(2+) homeostasis.
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Registered trials
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 Socratic graph.