ArticleScientific reports2016
A cholesterol-binding domain in STIM1 modulates STIM1-Orai1 physical and functional interactions.
Article in Scientific reports, 2016. 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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Who cites it
32 citing papers in PubMed.
- Mechanistic insights into Orai dynamics during pore opening.Channels (Austin, Tex.) · 2026Review
- DHHC21 is a STIM1 protein S-acyltransferase that modulates immune function in vivo.Journal of cell science · 2026Article
- STIM1-containing contact sites promote direct calcium flux from the endoplasmic reticulum to mitochondria.The EMBO journal · 2026Article
- STIM1 and lipid interactions at ER-PM contact sites.American journal of physiology. Cell physiology · 2025Review
- Analysis of cholesterol-recognition motifs of the plasma membrane CaJournal of bioenergetics and biomembranes · 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
- Article
- Roles of Cholesterol and PtdIns(4,5)PAdvances in experimental medicine and biology · 2023Review
- Regulatory mechanisms controlling store-operated calcium entry.Frontiers in physiology · 2023Review
- CRAC and SK Channels: Their Molecular Mechanisms Associated with Cancer Cell Development.Cancers · 2022Review
- 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
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
- Orai1 Boosts SK3 Channel Activation.Cancers · 2021Article
- Regulation of Store-Operated CaCells · 2021Review
- Endoplasmic Reticulum-Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling.International journal of molecular sciences · 2021Review
- The Orai Pore Opening Mechanism.International journal of molecular sciences · 2021Review
- Molecular Choreography and Structure of CaMembranes · 2020Review
- PHOSPHOINOSITIDES AND CALCIUM SIGNALING. A MARRIAGE ARRANGED IN ER-PM CONTACT SITES.Current opinion in physiology · 2020Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
STIM1 and Orai1 are the main components of a widely conserved Calcium influx pathway known as store-operated calcium entry (SOCE). STIM1 is a calcium sensor, which oligomerizes and activates Orai channels when calcium levels drop inside the endoplasmic reticulum (ER). The series of molecular rearrangements that STIM1 undergoes until final activation of Orai1 require the direct exposure of the STIM1 domain known as SOAR (Stim Orai Activating Region). In addition to these complex molecular rearrangements, other constituents like lipids at the plasma membrane, play critical roles orchestrating SOCE. PI(4,5)P2 and enriched cholesterol microdomains have been shown as important signaling platforms that recruit the SOCE machinery in steps previous to Orai1 activation. However, little is known about the molecular role of cholesterol once SOCE is activated. In this study we provide clear evidence that STIM1 has a cholesterol-binding domain located inside the SOAR region and modulates Orai1 channels. We demonstrate a functional association of STIM1 and SOAR to cholesterol, indicating a close proximity of SOAR to the inner layer of the plasma membrane. In contrast, the depletion of cholesterol induces the SOAR detachment from the plasma membrane and enhances its association to Orai1. These results are recapitulated with full length STIM1.
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