ArticleCirculation research2013
Adenylyl cyclase subtype-specific compartmentalization: differential regulation of L-type Ca2+ current in ventricular myocytes.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 81 citations in OpenAlex.
- A framework to map cAMP signalling nanodomains: phosphodiesterase-centred phosphoproteome-interactome networks (pPINs) in cardiac myocytes.Journal of molecular endocrinology · 2026Review
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- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
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- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Adenylyl cyclase isoforms 5 and 6 in the cardiovascular system: complex regulation and divergent roles.Frontiers in pharmacology · 2024Review
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Adenylyl cyclase isoform 1 contributes to sinoatrial node automaticity via functional microdomains.JCI insight · 2022Article
- Preferential Expression of CaBiomolecules · 2022Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Selectin-targeting glycosaminoglycan-peptide conjugate limits neutrophil-mediated cardiac reperfusion injury.Cardiovascular research · 2022Article
- Dual Activation of Phosphodiesterase 3 and 4 Regulates Basal Cardiac Pacemaker Function and Beyond.International journal of molecular sciences · 2021Review
- Review
- Does Transient Receptor Potential Vanilloid Type 1 Alleviate or Aggravate Pathological Myocardial Hypertrophy?Frontiers in pharmacology · 2021Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- AKAP5 complex facilitates purinergic modulation of vascular L-type CaNature communications · 2020Article
- Components of the GTraffic (Copenhagen, Denmark) · 2020Article
- Blockade of β-adrenergic signaling suppresses inflammasome and alleviates cardiac fibrosis.Annals of translational medicine · 2020Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleAdenylyl cyclase (AC) represents one of the principal molecules in the β-adrenergic receptor signaling pathway, responsible for the conversion of ATP to the second messenger, cAMP. AC types 5 (ACV) and 6 (ACVI) are the 2 main isoforms in the heart. Although highly homologous in sequence, these 2 proteins play different roles during the development of heart failure. Caveolin-3 is a scaffolding protein, integrating many intracellular signaling molecules in specialized areas called caveolae. In cardiomyocytes, caveolin is located predominantly along invaginations of the cell membrane known as t-tubules.
objectiveWe take advantage of ACV and ACVI knockout mouse models to test the hypothesis that there is distinct compartmentalization of these isoforms in ventricular myocytes. METHODS AND
resultsWe demonstrate that ACV and ACVI isoforms exhibit distinct subcellular localization. The ACVI isoform is localized in the plasma membrane outside the t-tubular region and is responsible for β1-adrenergic receptor signaling-mediated enhancement of the L-type Ca(2+) current (ICa,L) in ventricular myocytes. In contrast, the ACV isoform is localized mainly in the t-tubular region where its influence on ICa,L is restricted by phosphodiesterase. We further demonstrate that the interaction between caveolin-3 with ACV and phosphodiesterase is responsible for the compartmentalization of ACV signaling.
conclusionsOur results provide new insights into the compartmentalization of the 2 AC isoforms in the regulation of ICa,L in ventricular myocytes. Because caveolae are found in most mammalian cells, the mechanism of β- adrenergic receptor and AC compartmentalization may also be important for β-adrenergic receptor signaling in other cell types.
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