ArticlePloS one2014
Role of membrane microdomains in compartmentation of cAMP signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
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- Outlining the structure of cAMP compartments in Trypanosoma cruzi.Trends in parasitology · 2025Review
- Intersection of GPCR trafficking and cAMP signaling at endomembranes.The Journal of cell biology · 2025Review
- Cholesterol inhibits assembly and oncogenic activation of the EphA2 receptor.Communications biology · 2025Article
- Role of protein kinase A and A kinase anchoring proteins in buffering and compartmentation of cAMP signalling in human airway smooth muscle cells.British journal of pharmacology · 2024Article
- Cholesterol inhibits assembly and activation of the EphA2 receptor.bioRxiv : the preprint server for biology · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- CaPhysiological reviews · 2024Review
- Fluorescent biosensor imaging meets deterministic mathematical modelling: quantitative investigation of signalling compartmentalization.The Journal of physiology · 2023Review
- Article
- Subcellular second messenger networks drive distinct repellent-induced axon behaviors.Nature communications · 2023Article
- Quantitative phosphoproteomic analysis reveals unique cAMP signaling pools emanating from AC2 and AC6 in human airway smooth muscle cells.Frontiers in physiology · 2023Article
- Requirement of Zebrafish Adcy3a and Adcy5 in Melanosome Dispersion and Melanocyte Stripe Formation.International journal of molecular sciences · 2022Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses.Frontiers in immunology · 2022Article
- Extracellular cAMP-Adenosine Pathway Signaling: A Potential Therapeutic Target in Chronic Inflammatory Airway Diseases.Frontiers in immunology · 2022Review
- Phosphodiesterase 4 mediates interleukin-8-induced heterologous desensitization of the βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Bioengineering tools for probing intracellular events in T lymphocytes.WIREs mechanisms of disease · 2021Review
- Article
- Compartmentation of βBritish journal of pharmacology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Spatially restricting cAMP production to discrete subcellular locations permits selective regulation of specific functional responses. But exactly where and how cAMP signaling is confined is not fully understood. Different receptors and adenylyl cyclase isoforms responsible for cAMP production are not uniformly distributed between lipid raft and non-lipid raft domains of the plasma membrane. We sought to determine the role that these membrane domains play in organizing cAMP responses in HEK293 cells. The freely diffusible FRET-based biosensor Epac2-camps was used to measure global cAMP responses, while versions of the probe targeted to lipid raft (Epac2-MyrPalm) and non-raft (Epac2-CAAX) domains were used to monitor local cAMP production near the plasma membrane. Disruption of lipid rafts by cholesterol depletion selectively altered cAMP responses produced by raft-associated receptors. The results indicate that receptors associated with lipid raft as well as non-lipid raft domains can contribute to global cAMP responses. In addition, basal cAMP activity was found to be significantly higher in non-raft domains. This was supported by the fact that pharmacologic inhibition of adenylyl cyclase activity reduced basal cAMP activity detected by Epac2-CAAX but not Epac2-MyrPalm or Epac2-camps. Responses detected by Epac2-CAAX were also more sensitive to direct stimulation of adenylyl cyclase activity, but less sensitive to inhibition of phosphodiesterase activity. Quantitative modeling was used to demonstrate that differences in adenylyl cyclase and phosphodiesterase activities are necessary but not sufficient to explain compartmentation of cAMP associated with different microdomains of the plasma membrane.
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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.