ArticleScience signaling2016
Cholesterol modulates Orai1 channel function.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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
50 citing papers in PubMed, 92 citations in OpenAlex.
- Mechanistic insights into Orai dynamics during pore opening.Channels (Austin, Tex.) · 2026Review
- Schwann Cell Synthesized Cholesterol Orchestrates Peripheral Nerve Regeneration via Structural and IGF1-Dependent Signaling Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Quantitative Mapping of the Lipid Nanoenvironment around Transmembrane Proteins in Living Cells.ACS nano · 2026Article
- STIM1 and lipid interactions at ER-PM contact sites.American journal of physiology. Cell physiology · 2025Review
- S-acylation of CaChronic diseases and translational medicine · 2024Review
- Mitochondrial dysfunction in pancreatic acinar cells: mechanisms and therapeutic strategies in acute pancreatitis.Frontiers in immunology · 2024Review
- Article
- Cortisol Rapidly Facilitates Glucocorticoid Receptor Translocation to the Plasma Membrane in Primary Trout Hepatocytes.Biology · 2023Article
- CRAC and SK Channels: Their Molecular Mechanisms Associated with Cancer Cell Development.Cancers · 2022Review
- The sun, cholesterol and Orai1 conspire in melanoma.The EMBO journal · 2022Article
- Suppression of CaThe EMBO journal · 2022Article
- TRPV6 Regulation by Cis-22a and Cholesterol.Biomolecules · 2022Article
- Lipid Dyshomeostasis and Inherited Cerebellar Ataxia.Molecular neurobiology · 2022Review
- The Role of Lipids in CRAC Channel Function.Biomolecules · 2022Review
- Review
- Highlighting the Multifaceted Role of Orai1 N-Terminal- and Loop Regions for Proper CRAC Channel Functions.Cells · 2022Review
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
- Orai1 Boosts SK3 Channel Activation.Cancers · 2021Article
- Review
- Regulation of Store-Operated CaCells · 2021Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
STIM1 (stromal interaction molecule 1) and Orai proteins are the essential components of Ca(2+) release-activated Ca(2+) (CRAC) channels. We focused on the role of cholesterol in the regulation of STIM1-mediated Orai1 currents. Chemically induced cholesterol depletion enhanced store-operated Ca(2+) entry (SOCE) and Orai1 currents. Furthermore, cholesterol depletion in mucosal-type mast cells augmented endogenous CRAC currents, which were associated with increased degranulation, a process that requires calcium influx. Single point mutations in the Orai1 amino terminus that would be expected to abolish cholesterol binding enhanced SOCE to a similar extent as did cholesterol depletion. The increase in Orai1 activity in cells expressing these cholesterol-binding-deficient mutants occurred without affecting the amount in the plasma membrane or the coupling of STIM1 to Orai1. We detected cholesterol binding to an Orai1 amino-terminal fragment in vitro and to full-length Orai1 in cells. Thus, our data showed that Orai1 senses the amount of cholesterol in the plasma membrane and that the interaction of Orai1 with cholesterol inhibits its activity, thereby limiting SOCE.
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What OpenQuestion holds
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 OpenQuestion graph.