ArticleCirculation research2015
Genetic deletion of Rnd3/RhoE results in mouse heart calcium leakage through upregulation of protein kinase A signaling.
Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- RND3 Enhances Cardiac Glucose Metabolism Through Inhibiting ACAT1-Dependent PDHA1 Acetylation and Protects Against Ischemia-Reperfusion Injury.Circulation · 2026Article
- Immune sentinel function of nasal mucosal epithelial cells in allergic rhinitis: a review on barrier damage and inflammatory amplification loops regulated by calcium signalling.Frontiers in immunology · 2026Review
- Diabetes Advances Cardiomyocyte Senescence Through Interfering Rnd3 Expression and Function.Aging cell · 2025Article
- Rnd3 protects against doxorubicin-induced cardiotoxicity through inhibition of PANoptosis in a Rock1/Drp1/mitochondrial fission-dependent manner.Cell death & disease · 2025Article
- Association between albumin-corrected calcium and all-cause mortality in patients with heart failure: a retrospective study.Frontiers in cardiovascular medicine · 2025Article
- U-shaped association between serum calcium and in-hospital mortality in diabetes patients with congestive heart failure: a cohort study.Scientific reports · 2024Article
- Identification of New Markers of Angiogenic Sprouting Using Transcriptomics: New Role for RND3.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Rnd3 suppresses endothelial cell pyroptosis in atherosclerosis through regulation of ubiquitination of TRAF6.Clinical and translational medicine · 2023Article
- Landscape of circular RNAs in different types of lung cancer and an emerging role in therapeutic resistance (Review).International journal of oncology · 2023Article
- Fibroblast-specific activation of Rnd3 protects against cardiac remodeling in diabetic cardiomyopathy via suppression of Notch and TGF-β signaling.Theranostics · 2022Article
- Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating the PPARγ-UCP2 cascade.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Inhibiting miR-205 Alleviates Cardiac Ischemia/Reperfusion Injury by Regulating Oxidative Stress, Mitochondrial Function, and Apoptosis.Oxidative medicine and cellular longevity · 2021Article
- Identification and characterization of a new isoform of small GTPase RhoE.Communications biology · 2020Article
- Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene‑edited cardiomyocytes.International journal of molecular medicine · 2020Article
- Spatial and temporal tracking of cardiac exosomes in mouse using a nano-luciferase-CD63 fusion protein.Communications biology · 2020Article
- Investigation of leukocyteExperimental and therapeutic medicine · 2019Article
- Building Blood Vessels-One Rho GTPase at a Time.Cells · 2019Review
- Protein Phosphatase 2A Regulates Cardiac NaCirculation research · 2019Article
- RhoE Fine-Tunes Inflammatory Response in Myocardial Infarction.Circulation · 2019Article
- Stress Signaling JNK2 Crosstalk With CaMKII Underlies Enhanced Atrial Arrhythmogenesis.Circulation research · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleRnd3, a small Rho GTPase, is involved in the regulation of cell actin cytoskeleton dynamics, cell migration, and proliferation. The biological function of Rnd3 in the heart remains unexplored.
objectiveTo define the functional role of the Rnd3 gene in the animal heart and investigate the associated molecular mechanism. METHODS AND
resultsBy loss-of-function approaches, we discovered that Rnd3 is involved in calcium regulation in cardiomyocytes. Rnd3-null mice died at the embryonic stage with fetal arrhythmias. The deletion of Rnd3 resulted in severe Ca(2+) leakage through destabilized ryanodine receptor type 2 Ca(2+) release channels. We further found that downregulation of Rnd3 attenuated β2-adrenergic receptor lysosomal targeting and ubiquitination, which in turn resulted in the elevation of β2-adrenergic receptor protein levels leading to the hyperactivation of protein kinase A (PKA) signaling. The PKA activation destabilized ryanodine receptor type 2 channels. This irregular spontaneous Ca(2+) release can be curtailed by PKA inhibitor treatment. Increases in the PKA activity along with elevated cAMP levels were detected in Rnd3-null embryos, in neonatal rat cardiomyocytes, and noncardiac cell lines with Rnd3 knockdown, suggesting a general mechanism for Rnd3-mediated PKA signaling activation. β2-Adrenergic receptor blocker treatment reduced arrhythmia and improved cardiac function.
conclusionsRnd3 is a novel factor involved in intracellular Ca(2+) homeostasis regulation in the heart. Deficiency of the protein induces ryanodine receptor type 2 dysfunction by a mechanism that attenuates Rnd3-mediated β2-adrenergic receptor ubiquitination, which leads to the activation of PKA signaling. Increased PKA signaling in turn promotes ryanodine receptor type 2 hyperphosphorylation, which contributes to arrhythmogenesis and heart failure.
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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.