ArticleeLife2021
Dwarf open reading frame (DWORF) is a direct activator of the sarcoplasmic reticulum calcium pump SERCA.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Sarcolipin is a Conformation-Dependent Regulator of the Sarcoplasmic Reticulum Calcium Pump SERCA.The Journal of membrane biology · 2026Article
- Microprotein, macro-effect: DWORF as a therapeutic strategy in heart failure.Frontiers in cell and developmental biology · 2026Review
- The SERCA-PLN-DWORF axis in cardiometabolic disease: mechanisms and therapeutic perspectives.Cardiovascular diabetology · 2025Review
- MCARE enhances SERCA1 activity in fast-twitch muscle to maintain calcium handling and muscle integrity.Nature communications · 2025Article
- Allosteric Modulation of SERCA Pumps in Health and Disease: Structural Dynamics, Posttranslational Modifications, and Therapeutic Potential.Journal of molecular biology · 2025Review
- DWORF Gene Therapy Improves Cardiac Calcium Handling and Mitochondrial Function.Circulation research · 2025Article
- Structural Elements of Dwarf Open Reading Frame Required for Activation of the Sarco-Endoplasmic Reticulum Calcium Pump.Biochemistry · 2025Article
- Calcium-dependent levels of phospholamban pentamer in native heart membranes reflect interactions of monomers with calcium-free SERCA2a.Archives of biochemistry and biophysics · 2025Article
- Emerging roles for microproteins as critical regulators of endoplasmic reticulum function and cellular homeostasis.Seminars in cell & developmental biology · 2025Review
- The endoplasmic reticulum luminal CaPNAS nexus · 2025Article
- Phosphorylation of phospholamban promotes SERCA2a activation by dwarf open reading frame (DWORF).Cell calcium · 2024Article
- Regulation of cardiac calcium signaling by newly identified calcium pump modulators.Biochemical and biophysical research communications · 2023Article
- Microproteins-Discovery, structure, and function.Proteomics · 2023Review
- Positive Allosteric Modulators of SERCA Pump Restore Dendritic Spines and Rescue Long-Term Potentiation Defects in Alzheimer's Disease Mouse Model.International journal of molecular sciences · 2023Article
- Phospholamban pentamerization increases sensitivity and dynamic range of cardiac relaxation.Cardiovascular research · 2023Article
- Fluorescence lifetime FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators.Scientific reports · 2023Article
- Review
- Cardiac Plin5 interacts with SERCA2 and promotes calcium handling and cardiomyocyte contractility.Life science alliance · 2023Article
- FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators.Research square · 2023Article
- The Meeting of Micropeptides with Major CaMembranes · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The sarco-plasmic reticulum calcium pump (SERCA) plays a critical role in the contraction-relaxation cycle of muscle. In cardiac muscle, SERCA is regulated by the inhibitor phospholamban. A new regulator, dwarf open reading frame (DWORF), has been reported to displace phospholamban from SERCA. Here, we show that DWORF is a direct activator of SERCA, increasing its turnover rate in the absence of phospholamban. Measurement of in-cell calcium dynamics supports this observation and demonstrates that DWORF increases SERCA-dependent calcium reuptake. These functional observations reveal opposing effects of DWORF activation and phospholamban inhibition of SERCA. To gain mechanistic insight into SERCA activation, fluorescence resonance energy transfer experiments revealed that DWORF has a higher affinity for SERCA in the presence of calcium. Molecular modeling and molecular dynamics simulations provide a model for DWORF activation of SERCA, where DWORF modulates the membrane bilayer and stabilizes the conformations of SERCA that predominate during elevated cytosolic calcium.
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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.