ArticleProceedings of the National Academy of Sciences of the United States of America2015
Palmitoyl acyltransferase Aph2 in cardiac function and the development of cardiomyopathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Guidelines for measuring cardiac physiology in mice.American journal of physiology. Heart and circulatory physiology · 2018Guideline
- Protein lipidation in cardiovascular homeostasis, development, and disease.Clinical science (London, England : 1979) · 2026Review
- Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.Acta pharmaceutica Sinica. B · 2025Review
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- Valproate decreases transgenerationally blood pressure by affecting thyrotropin-releasing hormone promoter DNA methylation and gene expression in spontaneously hypertensive rat.Molecular and cellular biochemistry · 2025Article
- Genetic landscape of phospholamban cardiomyopathies.Frontiers in cell and developmental biology · 2025Review
- Regulation of post-translational modification of PD-L1 and associated opportunities for novel small-molecule therapeutics.Future medicinal chemistry · 2024Review
- Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation.Biochemical Society transactions · 2024Article
- Comprehensive Characterization of Endogenous Phospholamban Proteoforms Enabled by Photocleavable Surfactant and Top-down Proteomics.Analytical chemistry · 2023Article
- Current knowledge of protein palmitoylation in gliomas.Molecular biology reports · 2022Review
- Dynamic Expression of Palmitoylation Regulators across Human Organ Development and Cancers Based on Bioinformatics.Current issues in molecular biology · 2022Article
- Mapping the Proteoform Landscape of Five Human Tissues.Journal of proteome research · 2022Article
- Global identification of S-palmitoylated proteins and detection of palmitoylating (DHHC) enzymes in heart.Journal of molecular and cellular cardiology · 2021Article
- Increased novelty-induced locomotion, sensitivity to amphetamine, and extracellular dopamine in striatum of Zdhhc15-deficient mice.Translational psychiatry · 2021Article
- Sarcolipin alters SERCA1a interdomain communication by impairing binding of both calcium and ATP.Scientific reports · 2021Article
- Putative Role of Protein Palmitoylation in Cardiac Lipid-Induced Insulin Resistance.International journal of molecular sciences · 2020Review
- Sarcolipin Exhibits Abundant RNA Transcription and Minimal Protein Expression in Horse Gluteal Muscle.Veterinary sciences · 2020Article
- Control of protein palmitoylation by regulating substrate recruitment to a zDHHC-protein acyltransferase.Communications biology · 2020Article
- Palmitoylation: A Fatty Regulator of Myocardial Electrophysiology.Frontiers in physiology · 2020Review
- AKAP6 and phospholamban colocalize and interact in HEK-293T cells and primary murine cardiomyocytes.Physiological reports · 2019Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein palmitoylation regulates many aspects of cell function and is carried out by acyl transferases that contain zf-DHHC motifs. The in vivo physiological function of protein palmitoylation is largely unknown. Here we generated mice deficient in the acyl transferase Aph2 (Ablphilin 2 or zf-DHHC16) and demonstrated an essential role for Aph2 in embryonic/postnatal survival, eye development, and heart development. Aph2(-/-) embryos and pups showed cardiomyopathy and cardiac defects including bradycardia. We identified phospholamban, a protein often associated with human cardiomyopathy, as an interacting partner and a substrate of Aph2. Aph2-mediated palmitoylation of phospholamban on cysteine 36 differentially alters its interaction with PKA and protein phosphatase 1 α, augmenting serine 16 phosphorylation, and regulates phospholamban pentamer formation. Aph2 deficiency results in phospholamban hypophosphorylation, a hyperinhibitory form. Ablation of phospholamban in Aph2(-/-) mice histologically and functionally alleviated the heart defects. These findings establish Aph2 as a critical in vivo regulator of cardiac function and reveal roles for protein palmitoylation in the development of other organs including eyes.
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