ArticleJournal of molecular and cellular cardiology2016
BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes.
Article in Journal of molecular and cellular cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 63 citations in OpenAlex.
- Deletion of Murine Endothelial <italic>Bag3</italic> Alters the Cellular Proteome among Organs of Origin.Journal of vascular research · 2026Article
- The beta1-adrenergic receptor in the heart.Cell death discovery · 2025Review
- Dilated Cardiomyopathy: A NovelJournal of cardiovascular development and disease · 2025Article
- Article
- BAG3 localizes to mitochondria in cardiac fibroblasts and regulates mitophagy.American journal of physiology. Heart and circulatory physiology · 2024Article
- Dysregulated Autophagy and Sarcomere Dysfunction in Patients With Heart Failure With Co-Occurrence of P63A and P380SJournal of the American Heart Association · 2023Article
- Bag3 Regulates Mitochondrial Function and the Inflammasome Through Canonical and Noncanonical Pathways in the Heart.JACC. Basic to translational science · 2023Article
- Skeletal Muscle-SpecificInternational journal of molecular sciences · 2023Article
- CoexistingThe Journal of innovations in cardiac rhythm management · 2023Article
- BAG3: Nature's Quintessential Multi-Functional Protein Functions as a Ubiquitous Intra-Cellular Glue.Cells · 2023Review
- Genetics of BAG3: A Paradigm for Developing Precision Therapies for Dilated Cardiomyopathies.Journal of the American Heart Association · 2022Review
- BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson's disease.Annals of translational medicine · 2022Article
- BAG3 Regulation of RAB35 Mediates the Endosomal Sorting Complexes Required for Transport/Endolysosome Pathway and Tau Clearance.Biological psychiatry · 2022Article
- The HVCN1 voltage-gated proton channel contributes to pH regulation in canine ventricular myocytes.The Journal of physiology · 2022Article
- MicroRNA regulation of BAG3.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- The role of BAG3 in health and disease: A "Magic BAG of Tricks".Journal of cellular biochemistry · 2022Review
- Calenduloside E suppresses calcium overload by promoting the interaction between L-type calcium channels and Bcl2-associated athanogene 3 to alleviate myocardial ischemia/reperfusion injury.Journal of advanced research · 2021Article
- Towards precision medicine in heart failure.Nature reviews. Cardiology · 2021Review
- Therapeutic targeting of BAG3: considering its complexity in cancer and heart disease.The Journal of clinical investigation · 2021Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 2 countries.
Funding
Abstract
Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na(+)-K(+)-ATPase and L-type Ca(2+) channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca(2+) channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca(2+)]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca(2+) current (ICa) and sarcoplasmic reticulum (SR) Ca(2+) content but not Na(+)/Ca(2+) exchange current (INaCa) or SR Ca(2+) uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyryl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca(2+) entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca(2+) channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure.
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Registered trials
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