ArticleCirculation research2022
AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR.
Article in Circulation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 57 citations in OpenAlex.
- Exploring the role of CaMKII in exercise-induced cardioprotection.Human cell · 2026Review
- Phosphodiesterase 8 regulation of excitation-contraction coupling as a target for cardiovascular disease: is it my turn now?American journal of physiology. Heart and circulatory physiology · 2026Review
- Activated CaMKIIδ translocates to the RyR nanodomain in cardiomyocytes.Cardiovascular research · 2025Article
- Identification of a Small Secretoneurin Derivative That Inhibits CaMKIIδ Activity.Journal of cellular and molecular medicine · 2025Article
- CaInflammation and regeneration · 2025Review
- Glyoxal is a superior fixative to formaldehyde in promoting antigenicity and structural integrity in murine cardiac tissues.Journal of molecular and cellular cardiology plus · 2025Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Protective role of triiodothyronine in sepsis‑induced cardiomyopathy through phospholamban downregulation.International journal of molecular medicine · 2025Article
- The role of A-kinase anchoring proteins in cardiovascular diseases and recent advances.Frontiers in cell and developmental biology · 2025Review
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Tripartite interactions of PKA catalytic subunit and C-terminal domains of cardiac CaBMC biology · 2024Article
- Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Gallic acid: a dietary metabolite's therapeutic potential in the management of atherosclerotic cardiovascular disease.Frontiers in pharmacology · 2024Review
- Irisin attenuates vascular remodeling in hypertensive mice induced by Ang II by suppressing CaInternational journal of biological sciences · 2024Article
- M-type pyruvate kinase 2 (PKM2) tetramerization alleviates the progression of right ventricle failure by regulating oxidative stress and mitochondrial dynamics.Journal of translational medicine · 2023Article
- Article
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- [Enhanced endoplasmic reticulum RyR1 receptor phosphorylation leads to diaphragmatic dysfunction in septic rats].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- CaMKII regulates the proteins TPM1 and MYOM2 and promotes diacetylmorphine-induced abnormal cardiac rhythms.Scientific reports · 2023Article
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22 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundThe sarcoplasmic reticulum (SR) Ca
methodsA role for AKAP18δ (A-kinase anchoring protein 18δ) in CaMKIIδ anchoring and regulation was analyzed by bioinformatics, peptide arrays, cell-permeant peptide technology, immunoprecipitations, pull downs, transfections, immunoblotting, proximity ligation, FRET-based CaMKII activity and ELISA-based assays, whole cell and SR vesicle fluorescence imaging, high-resolution microscopy, adenovirus transduction, adenoassociated virus injection, structural modeling, surface plasmon resonance, and alpha screen technology.
resultsOur results show that AKAP18δ anchors and directly regulates CaMKIIδ activity at SERCA2-PLN and RYR, via 2 distinct AKAP18δ regions. An N-terminal region (AKAP18δ-N) inhibited CaMKIIδ through binding of a region homologous to the natural CaMKII inhibitor peptide and the Thr17-PLN region. AKAP18δ-N also bound CaM, introducing a second level of control. Conversely, AKAP18δ-C, which shares homology to neuronal CaMKIIα activator peptide (N2B-s), activated CaMKIIδ by lowering the apparent Ca
conclusionsAKAP18δ anchors and functionally regulates CaMKII activity at PLN-SERCA2 and RYR, indicating a crucial role of AKAP18δ in regulation of the heartbeat. To our knowledge, this is the first protein shown to enhance CaMKII activity in heart and also the first AKAP (A-kinase anchoring protein) reported to anchor a CaMKII isoform, defining AKAP18δ also as a CaM-KAP.
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