ArticleeLife2021
The role of sigma 1 receptor in organization of endoplasmic reticulum signaling microdomains.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 60 citations in OpenAlex.
- Autophagy in Alzheimer's Disease: Mechanisms, Clinical Trials, and Horizons.Neuro-degenerative diseases · 2026Review
- The Sigma1 ER membrane receptor promotes structural protein folding and genome packaging of dengue virus.PLoS pathogens · 2026Article
- Low 5HTJournal of neurochemistry · 2026Review
- Pridopidine Protects ALS Patient-Derived Neural Progenitor Cells via Sigma-1 Receptor Activation.International journal of molecular sciences · 2026Article
- Mitochondria-endoplasmic reticulum contact sites in hepatocytic senescence.Cellular & molecular biology letters · 2026Review
- The lipid-modulating effect of berberine in hyperlipidemic ApoE-/- mice.Frontiers in pharmacology · 2026Article
- SigmaR1 is an auxiliary translocon factor with lipid-binding activity that regulates protein and lipid droplet homeostasis.Nature communications · 2025Article
- Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Sigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles.Cancer biology & therapy · 2025Article
- Sigma-1 Receptor Ligands for CNS Cancer Treatment.CNS drugs · 2025Review
- Pathophysiology and potential multimodal therapeutic strategies for IC/BPS.Nature reviews. Urology · 2025Review
- Choline-An Essential Nutrient with Health Benefits and a Signaling Molecule.International journal of molecular sciences · 2025Review
- Uncovering the Mechanisms of Intracellular Membrane Trafficking by Reconstituted Membrane Systems.Membranes · 2025Review
- Protein interactions, calcium, phosphorylation, and cholesterol modulate CFTR cluster formation on membranes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.ACS pharmacology & translational science · 2025Review
- Sigma-1 receptor exerts protective effects on ameliorating nephrolithiasis by modulating endoplasmic reticulum-mitochondrion association and inhibiting endoplasmic reticulum stress-induced apoptosis in renal tubular epithelial cells.Redox report : communications in free radical research · 2024Article
- Comprehensive Analysis of Age- and Sex-Related Expression of the Chaperone Protein Sigma-1R in the Mouse Brain.Brain sciences · 2024Article
- 10th European Calcium Society symposium: The Ca2+-signaling toolkit in cell function, health and disease.Biology open · 2024Review
- Benzomorphan and non-benzomorphan agonists differentially alter sigma-1 receptor quaternary structure, as does types of cellular stress.Cellular and molecular life sciences : CMLS · 2024Article
- Structure-Based Modeling of Sigma 1 Receptor Interactions with Ligands and Cholesterol and Implications for Its Biological Function.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Sigma 1 receptor (S1R) is a 223-amino-acid-long transmembrane endoplasmic reticulum (ER) protein. S1R modulates activity of multiple effector proteins and is a well-established drug target. However, signaling functions of S1R in cells are poorly understood. Here, we test the hypothesis that biological activity of S1R in cells can be explained by its ability to interact with cholesterol and to form cholesterol-enriched microdomains in the ER membrane. By performing experiments in reduced reconstitution systems, we demonstrate direct effects of cholesterol on S1R clustering. We identify a novel cholesterol-binding motif in the transmembrane region of human S1R. Mutations of this motif impair association of recombinant S1R with cholesterol beads, affect S1R clustering in vitro and disrupt S1R subcellular localization. We demonstrate that S1R-induced membrane microdomains have increased local membrane thickness and that increased local cholesterol concentration and/or membrane thickness in these microdomains can modulate signaling of inositol-requiring enzyme 1α in the ER. Further, S1R agonists cause disruption of S1R clusters, suggesting that biological activity of S1R agonists is linked to remodeling of ER membrane microdomains. Our results provide novel insights into S1R-mediated signaling mechanisms in cells.
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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.