ArticleThe Journal of biological chemistry2014
A direct interaction between the sigma-1 receptor and the hERG voltage-gated K+ channel revealed by atomic force microscopy and homogeneous time-resolved fluorescence (HTRF®).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- The landscape of cocaine cytotoxicity and the role of sigma-1 receptor modulation and adulterant synergism.Archives of toxicology · 2026Review
- Sigma-1 Receptor Specific Biological Functions, Protective Role, and Therapeutic Potential in Cardiovascular Diseases.Cardiovascular toxicology · 2025Review
- Safe and Efficient Sigma1 Ligand: A Potential Drug Candidate for Multiple Sclerosis.International journal of molecular sciences · 2022Article
- Sigma non-opioid receptor 1 is a potential therapeutic target for long QT syndrome.Nature cardiovascular research · 2022Article
- Potassium and Calcium Channel Complexes as Novel Targets for Cancer Research.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Intracellular dynamics of the Sigma-1 receptor observed with super-resolution imaging microscopy.PloS one · 2022Article
- Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders.Neuroscience and biobehavioral reviews · 2022Review
- Article
- Sigma-1 receptor activation-induced glycolytic ATP production and endothelial barrier enhancement.Microcirculation (New York, N.Y. : 1994) · 2020Article
- Is the sigma-1 receptor a potential pharmacological target for cardiac pathologies? A systematic review.International journal of cardiology. Heart & vasculature · 2020Review
- Partners in Crime: Towards New Ways of Targeting Calcium Channels.International journal of molecular sciences · 2019Review
- The Molecular Function of σ Receptors: Past, Present, and Future.Trends in pharmacological sciences · 2019Review
- Molecular Interplay Between the Sigma-1 Receptor, Steroids, and Ion Channels.Frontiers in pharmacology · 2019Review
- Pharmacophore and docking-based sequential virtual screening for the identification of novel Sigma 1 receptor ligands.Bioinformation · 2019Article
- The Sigma-1 Receptor: When Adaptive Regulation of Cell Electrical Activity Contributes to Stimulant Addiction and Cancer.Frontiers in neuroscience · 2019Review
- Small-Molecule Modulators of Sigma1 and Sigma2/TMEM97 in the Context of Cancer: Foundational Concepts and Emerging Themes.Frontiers in pharmacology · 2019Review
- Neuronal Sigma-1 Receptors: Signaling Functions and Protective Roles in Neurodegenerative Diseases.Frontiers in neuroscience · 2019Review
- Cardiac Dysfunction in the Sigma 1 Receptor Knockout Mouse Associated With Impaired Mitochondrial Dynamics and Bioenergetics.Journal of the American Heart Association · 2018Article
- TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process.Frontiers in pharmacology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The sigma-1 receptor is an endoplasmic reticulum chaperone protein, widely expressed in central and peripheral tissues, which can translocate to the plasma membrane and modulate the function of various ion channels. The human ether-à-go-go-related gene encodes hERG, a cardiac voltage-gated K(+) channel that is abnormally expressed in many human cancers and is known to interact functionally with the sigma-1 receptor. Our aim was to investigate the nature of the interaction between the sigma-1 receptor and hERG. We show that the two proteins can be co-isolated from a detergent extract of stably transfected HEK-293 cells, consistent with a direct interaction between them. Atomic force microscopy imaging of the isolated protein confirmed the direct binding of the sigma-1 receptor to hERG monomers, dimers, and tetramers. hERG dimers and tetramers became both singly and doubly decorated by sigma-1 receptors; however, hERG monomers were only singly decorated. The distribution of angles between pairs of sigma-1 receptors bound to hERG tetramers had two peaks, at ∼90 and ∼180° in a ratio of ∼2:1, indicating that the sigma-1 receptor interacts with hERG with 4-fold symmetry. Homogeneous time-resolved fluorescence (HTRF®) allowed the detection of the interaction between the sigma-1 receptor and hERG within the plane of the plasma membrane. This interaction was resistant to sigma ligands, but was decreased in response to cholesterol depletion of the membrane. We suggest that the sigma-1 receptor may bind to hERG in the endoplasmic reticulum, aiding its assembly and trafficking to the plasma membrane.
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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.