ArticleProceedings of the National Academy of Sciences of the United States of America2018
Phosphatases control PKA-dependent functional microdomains at the outer mitochondrial membrane.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Phosphatases Control the Duration and Range of cAMP/PKA Microdomains.Function (Oxford, England) · 2025Article
- An ALPK3 truncation variant causing autosomal dominant hypertrophic cardiomyopathy is partially rescued by mavacamten.Scientific reports · 2025Article
- Cyclic AMP induces reversible EPAC1 condensates that regulate histone transcription.Nature communications · 2023Article
- Article
- Disruption of mitochondria-sarcoplasmic reticulum microdomain connectomics contributes to sinus node dysfunction in heart failure.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Abnormal Cyclic Nucleotide Signaling at the Outer Mitochondrial Membrane In Sympathetic Neurons During the Early Stages of Hypertension.Hypertension (Dallas, Tex. : 1979) · 2022Article
- A multiscale model of the regulation of aquaporin 2 recycling.NPJ systems biology and applications · 2022Article
- Inhibition of PDE4 by apremilast attenuates skin fibrosis through directly suppressing activation of M1 and T cells.Acta pharmacologica Sinica · 2022Article
- Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses.Small GTPases · 2022Article
- Multi-Omics Approach Profiling Metabolic Remodeling in Early Systolic Dysfunction and in Overt Systolic Heart Failure.International journal of molecular sciences · 2021Article
- Dynamic FRET-FLIM based screening of signal transduction pathways.Scientific reports · 2021Article
- Metabolic Remodeling and Implicated Calcium and Signal Transduction Pathways in the Pathogenesis of Heart Failure.International journal of molecular sciences · 2021Review
- PKA compartmentalization links cAMP signaling and autophagy.Cell death and differentiation · 2021Article
- Cholesterol Activates Cyclic AMP Signaling in Metaplastic Acinar Cells.Metabolites · 2021Article
- Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Insight into the Interactome of Intramitochondrial PKA Using Biotinylation-Proximity Labeling.International journal of molecular sciences · 2020Article
- Multi-Compartment, Early Disruption of cGMP and cAMP Signalling in Cardiac Myocytes from theInternational journal of molecular sciences · 2020Article
- A kinase cascade on the yeast lysosomal vacuole regulates its membrane dynamics: conserved kinase Env7 is phosphorylated by casein kinase Yck3.The Journal of biological chemistry · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Evidence supporting the heterogeneity in cAMP and PKA signaling is rapidly accumulating and has been largely attributed to the localization or activity of adenylate cyclases, phosphodiesterases, and A-kinase-anchoring proteins in different cellular subcompartments. However, little attention has been paid to the possibility that, despite homogeneous cAMP levels, a major heterogeneity in cAMP/PKA signaling could be generated by the spatial distribution of the final terminators of this cascade, i.e., the phosphatases. Using FRET-based sensors to monitor cAMP and PKA-dependent phosphorylation in the cytosol and outer mitochondrial membrane (OMM) of primary rat cardiomyocytes, we demonstrate that comparable cAMP increases in these two compartments evoke higher levels of PKA-dependent phosphorylation in the OMM. This difference is most evident for small, physiological increases of cAMP levels and with both OMM-located probes and endogenous OMM proteins. We demonstrate that this disparity depends on differences in the rates of phosphatase-dependent dephosphorylation of PKA targets in the two compartments. Furthermore, we show that the activity of soluble phosphatases attenuates PKA-driven activation of the cAMP response element-binding protein while concurrently enhancing PKA-dependent mitochondrial elongation. We conclude that phosphatases can sculpt functionally distinct cAMP/PKA domains even in the absence of gradients or microdomains of this messenger. We present a model that accounts for these unexpected results in which the degree of PKA-dependent phosphorylation is dictated by both the subcellular distribution of the phosphatases and the different accessibility of membrane-bound and soluble phosphorylated substrates to the cytosolic enzymes.
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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.