ArticleNature chemical biology2021
Spatial decoding of endosomal cAMP signals by a metastable cytoplasmic PKA network.
Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- GPCR-selective effects of endocytosis on cellular signaling through the cAMP/PKA cascade.The Journal of biological chemistry · 2026Article
- Lysosomal down-regulation of the mu opioid receptor is opposed by the Retromer complex.Science advances · 2026Article
- Structure-Encoded Location Biased Signaling in a Class B GPCR: Focus on the PTH Type 1 Receptor.Handbook of experimental pharmacology · 2026Review
- Role of Neuronal Cholecystokinin Receptor: An Emerging Therapeutic Target for Ameliorating Neurological Diseases.Molecular neurobiology · 2025Review
- Probing spatiotemporally organized GPCR signaling using genetically encoded molecular tools.Experimental & molecular medicine · 2025Review
- Plasma membrane rather than endosomal Gq signaling drives transcriptional activity by the viral chemokine receptor US28 in glioblastoma.bioRxiv : the preprint server for biology · 2025Article
- Deciphering complexity of GPCR signaling and modulation: implications and perspectives for drug discovery.Clinical science (London, England : 1979) · 2025Review
- Intersection of GPCR trafficking and cAMP signaling at endomembranes.The Journal of cell biology · 2025Review
- An engineered trafficking biosensor reveals a role for DNAJC13 in DOR downregulation.Nature chemical biology · 2025Article
- A massively parallel reporter assay library to screen short synthetic promoters in mammalian cells.Nature communications · 2024Article
- Spatial organization of adenylyl cyclase and its impact on dopamine signaling in neurons.Nature communications · 2024Article
- "Radical" differences between two FLIM microscopes affect interpretation of cell signaling dynamics.iScience · 2024Article
- Molecular determinants and signaling effects of PKA RIα phase separation.Molecular cell · 2024Article
- Endosome positioning coordinates spatially selective GPCR signaling.Nature chemical biology · 2024Article
- Arrestin-dependent nuclear export of phosphodiesterase 4D promotes GPCR-induced nuclear cAMP signaling required for learning and memory.Science signaling · 2023Article
- Using the Proteomics Toolbox to Resolve Topology and Dynamics of Compartmentalized cAMP Signaling.International journal of molecular sciences · 2023Review
- Soluble cyclase-mediated nuclear cAMP synthesis is sufficient for cell proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The psychosis risk factorbioRxiv : the preprint server for biology · 2023Article
- Article
- Location bias contributes to functionally selective responses of biased CXCR3 agonists.Nature communications · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
G-protein-coupled receptor-regulated cAMP production from endosomes can specify signaling to the nucleus by moving the source of cAMP without changing its overall amount. How this is possible remains unknown because cAMP gradients dissipate over the nanoscale, whereas endosomes typically localize micrometers from the nucleus. We show that the key location-dependent step for endosome-encoded transcriptional control is nuclear entry of cAMP-dependent protein kinase (PKA) catalytic subunits. These are sourced from punctate accumulations of PKA holoenzyme that are densely distributed in the cytoplasm and titrated by global cAMP into a discrete metastable state, in which catalytic subunits are bound but dynamically exchange. Mobile endosomes containing activated receptors collide with the metastable PKA puncta and pause in close contact. We propose that these properties enable cytoplasmic PKA to act collectively like a semiconductor, converting nanoscale cAMP gradients generated from endosomes into microscale elevations of free catalytic subunits to direct downstream signaling.
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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.