ArticleProceedings of the National Academy of Sciences of the United States of America2006
STIM1 has a plasma membrane role in the activation of store-operated Ca(2+) channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
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Who cites it
158 citing papers in PubMed, 301 citations in OpenAlex.
- STIM1-dependent treg dysfunction promotes cardiometabolic HFpEF: insights from patients and animal studies.Cardiovascular diabetology · 2026Article
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- Review
- Context-dependent dysregulation of store-operated calcium channels in head and neck squamous cell carcinoma.PloS one · 2026Article
- Junctophilin-2 Regulates Store-Operated Calcium Entry to Drive Cardiac Fibroblast Activation, Fibrotic Repair, and Angiogenesis After Myocardial Infarction.Circulation · 2025Article
- Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders.Discover mental health · 2025Article
- OPEN STOMATA 1 phosphorylates CYCLIC NUCLEOTIDE-GATED CHANNELs to trigger Ca2+ signaling for abscisic acid-induced stomatal closure in Arabidopsis.The Plant cell · 2024Article
- Essential role of N-terminal SAM regions in STIM1 multimerization and function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- STIM2 regulates NMDA receptor endocytosis that is induced by short-term NMDA receptor overactivation in cortical neurons.Cellular and molecular life sciences : CMLS · 2023Article
- The CaBiomolecules · 2023Review
- Article
- Control of STIM and Orai function by post-translational modifications.Cell calcium · 2022Review
- STIM1-dependent peripheral coupling governs the contractility of vascular smooth muscle cells.eLife · 2022Article
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
- Role of Store-Operated CaBiomolecules · 2021Review
- Upregulated SOCC and IP3R calcium channels and subsequent elevated cytoplasmic calcium signaling promote nonalcoholic fatty liver disease by inhibiting autophagy.Molecular and cellular biochemistry · 2021Article
- Store-Operated Calcium Entry in the Cardiovascular System.Advances in experimental medicine and biology · 2021Review
- Store-Operated Calcium Channels as Drug Target in Gastroesophageal Cancers.Frontiers in pharmacology · 2021Review
- Transmembrane Domain 3 (TM3) Governs Orai1 and Orai3 Pore Opening in an Isoform-Specific Manner.Frontiers in cell and developmental biology · 2021Article
- Single-cell melanoma transcriptomes depicting functional versatility and clinical implications of STIM1 in the tumor microenvironment.Theranostics · 2021Article
98 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Receptor-induced Ca(2+) signals are key to the function of all cells and involve release of Ca(2+) from endoplasmic reticulum (ER) stores, triggering Ca(2+) entry through plasma membrane (PM) "store-operated channels" (SOCs). The identity of SOCs and their coupling to store depletion remain molecular and mechanistic mysteries. The single transmembrane-spanning Ca(2+)-binding protein, STIM1, is necessary in this coupling process and is proposed to function as an ER Ca(2+) sensor to provide the trigger for SOC activation. Here we reveal that, in addition to being an ER Ca(2+) sensor, STIM1 functions within the PM to control operation of the Ca(2+) entry channel itself. Increased expression levels of STIM1 correlate with a gain in function of Ca(2+) release-activated Ca(2+) (CRAC) channel activity. Point mutation of the N-terminal EF hand transforms the CRAC channel current (I(CRAC)) into a constitutively active, Ca(2+) store-independent mode. Mutants in the EF hand and cytoplasmic C terminus of STIM1 alter operational parameters of CRAC channels, including pharmacological profile and inactivation properties. Last, Ab externally applied to the STIM1 N-terminal EF hand blocks both I(CRAC) in hematopoietic cells and SOC-mediated Ca(2+) entry in HEK293 cells, revealing that STIM1 has an important functional presence within the PM. The results reveal that, in addition to being an ER Ca(2+) sensor, STIM1 functions within the PM to exert control over the operation of SOCs. As a cell surface signaling protein, STIM1 represents a key pharmacological target to control fundamental Ca(2+)-regulated processes including secretion, contraction, metabolism, cell division, and apoptosis.
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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.