ArticleNature medicine2013
Noncanonical EF-hand motif strategically delays Ca2+ buffering to enhance cardiac performance.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 39 citations in OpenAlex.
- Myofilament-based physiological regulatory compensation preserves diastolic function in failing hearts with severe Ca2+ handling deficits.JCI insight · 2024Article
- Nucleus Mechanosensing in Cardiomyocytes.International journal of molecular sciences · 2023Review
- A perinuclear calcium compartment regulates cardiac myocyte hypertrophy.Journal of molecular and cellular cardiology · 2022Article
- Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice.Nature communications · 2022Article
- Structural Changes beyond the EF-Hand Contribute to Apparent Calcium Binding Affinities: Insights from Parvalbumins.The journal of physical chemistry. B · 2021Article
- Advancing physiological maturation in human induced pluripotent stem cell-derived cardiac muscle by gene editing an inducible adult troponin isoform switch.Stem cells (Dayton, Ohio) · 2020Article
- Understanding the mammalian TRAP complex function(s).Open biology · 2020Review
- Dysregulation of Calcium Handling in Duchenne Muscular Dystrophy-Associated Dilated Cardiomyopathy: Mechanisms and Experimental Therapeutic Strategies.Journal of clinical medicine · 2020Review
- Force and Calcium Transients Analysis in Human Engineered Heart Tissues Reveals Positive Force-Frequency Relation at Physiological Frequency.Stem cell reports · 2020Article
- Cytosolic CaCold Spring Harbor perspectives in biology · 2020Review
- Cytoplasmic nucleic acid-based XNAs directly enhance live cardiac cell function by a CaJournal of molecular and cellular cardiology · 2019Article
- Gene Transfer of Calcium-Binding Proteins into Adult Cardiac Myocytes.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2017Article
- Understanding Ion Binding Affinity and Selectivity in β-Parvalbumin Using Molecular Dynamics and Mean Spherical Approximation Theory.The journal of physical chemistry. B · 2016Article
- Designing proteins to combat disease: Cardiac troponin C as an example.Archives of biochemistry and biophysics · 2016Review
- Effects of Modified Parvalbumin EF-Hand Motifs on Cardiac Myocyte Contractile Function.Biophysical journal · 2016Article
- Microtubule-Mediated Misregulation of Junctophilin-2 Underlies T-Tubule Disruptions and Calcium Mishandling inJACC. Basic to translational science · 2016Article
- Ophiopogonin D maintains Ca2+ homeostasis in rat cardiomyocytes in vitro by upregulating CYP2J3/EETs and suppressing ER stress.Acta pharmacologica Sinica · 2016Article
- In Vivo Analysis of Troponin C Knock-In (A8V) Mice: Evidence that TNNC1 Is a Hypertrophic Cardiomyopathy Susceptibility Gene.Circulation. Cardiovascular genetics · 2015Article
- Mitochondrial flash as a novel biomarker of mitochondrial respiration in the heart.American journal of physiology. Heart and circulatory physiology · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
EF-hand proteins are ubiquitous in cell signaling. Parvalbumin (Parv), the archetypal EF-hand protein, is a high-affinity Ca(2+) buffer in many biological systems. Given the centrality of Ca(2+) signaling in health and disease, EF-hand motifs designed to have new biological activities may have widespread utility. Here, an EF-hand motif substitution that had been presumed to destroy EF-hand function, that of glutamine for glutamate at position 12 of the second cation binding loop domain of Parv (ParvE101Q), markedly inverted relative cation affinities: Mg(2+) affinity increased, whereas Ca(2+) affinity decreased, forming a new ultra-delayed Ca(2+) buffer with favorable properties for promoting cardiac relaxation. In therapeutic testing, expression of ParvE101Q fully reversed the severe myocyte intrinsic contractile defect inherent to expression of native Parv and corrected abnormal myocardial relaxation in diastolic dysfunction disease models in vitro and in vivo. Strategic design of new EF-hand motif domains to modulate intracellular Ca(2+) signaling could benefit many biological systems with abnormal Ca(2+) handling, including the diseased heart.
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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.