ArticlePloS one2012
Palmitoylation regulates intracellular trafficking of β2 adrenergic receptor/arrestin/phosphodiesterase 4D complexes in cardiomyocytes.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- 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
- The role of protein S-acylation in vascular injury associated with metabolic disorders.Frontiers in endocrinology · 2025Review
- Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation.Biochemical Society transactions · 2024Article
- The dynamics of agonist-βNature chemistry · 2023Article
- Metabolically driven maturation of human-induced-pluripotent-stem-cell-derived cardiac microtissues on microfluidic chips.Nature biomedical engineering · 2022Article
- Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential.International journal of molecular sciences · 2022Review
- Regulation of Dynamic Protein S-Acylation.Frontiers in molecular biosciences · 2021Review
- Palmitoylation: A Fatty Regulator of Myocardial Electrophysiology.Frontiers in physiology · 2020Review
- Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in βCell reports · 2018Article
- Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies.Chemical reviews · 2018Article
- Palmitoylation as a Functional Regulator of Neurotransmitter Receptors.Neural plasticity · 2018Review
- Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications.Frontiers in physiology · 2017Review
- Multifactorial Regulation of G Protein-Coupled Receptor Endocytosis.Biomolecules & therapeutics · 2017Review
- S-Palmitoylation of a Novel Site in the β2-Adrenergic Receptor Associated with a Novel Intracellular Itinerary.The Journal of biological chemistry · 2016Article
- Insulin induces IRS2-dependent and GRK2-mediated β2AR internalization to attenuate βAR signaling in cardiomyocytes.Cellular signalling · 2015Article
- Temporal response of ectopic activity in guinea pig ventricular myocardium in response to isoproterenol and acetylcholine.Frontiers in physiology · 2015Article
- Trafficking of β-Adrenergic Receptors: Implications in Intracellular Receptor Signaling.Progress in molecular biology and translational science · 2015Review
- Compartmentalization of β-adrenergic signals in cardiomyocytes.Trends in cardiovascular medicine · 2013Review
- Volume overload induces differential spatiotemporal regulation of myocardial soluble guanylyl cyclase in eccentric hypertrophy and heart failure.Journal of molecular and cellular cardiology · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
β(2) adrenergic receptor (β(2)AR) is a prototypical G-protein coupled receptor that stimulates the classic cAMP-protein kinase A (PKA) signaling pathway. Recent studies indicate that the cAMP-PKA activities are spatiotemporally regulated in part due to dynamic association of β(2)AR with phosphodiesterase 4D (PDE4D), a group of cAMP degradation enzymes. Here, we demonstrate that in cardiomyocytes, palmitoylation of β(2)AR, the covalent acylation of cysteine residue 341, plays a critical role in shaping subcellular cAMP-PKA activities in cardiomyocytes via regulating β(2)AR association with arrestin/PDE4D. Replacing cysteine 341 on β(2)AR with alanine (C341A) leads to an impaired binding to β arrestin 2. Surprisingly, the C341A mutant is able to internalize via an arrestin-independent pathway at saturated concentration of agonist stimulation; the internalization becomes caveolae-dependent and requires dynamin GTPase. However, the impaired binding to β arrestin 2 also leads to an impaired recruitment of PDE4D to the C341A mutant. Thus, the mutant C341A β(2)AR is transported alone from the plasma membrane to the endosome without recruiting PDE4D. This alteration leads to an enhanced cytoplasmic cAMP signal for PKA activation under β(2)AR stimulation. Functionally, Mutation of the C341 residue or inhibition of palmitoylation modification of β(2)AR enhances the receptor-induced PKA activities in the cytoplasm and increases in myocyte contraction rate. Our data reveal a novel function of palmitoylation in shaping subcellular cAMP-PKA signaling in cardiomyocytes via modulating the recruitment of β arrestin 2-PDE4D complexes to the agonist-stimulated β(2)AR.
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Registered trials
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.