ArticleNature communications2023
Membranes prime the RapGEF EPAC1 to transduce cAMP signaling.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- The Synaptic Clock: SynGAP1 as a Molecular Timer of Postsynaptic Density Consolidation.Biomolecules · 2026Review
- Sonoepigenetic Modification Mechanoprimes Early Osteogenic Commitment in Mesenchymal Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ubiquitylation-dependent Rap2 activation regulates lamellipodia dynamics during cell migration.Journal of cell science · 2025Article
- Exploring the Connection Between BDNF/TrkB and AC/cAMP/PKA/CREB Signaling Pathways: Potential for Neuroprotection and Therapeutic Targets for Neurological Disorders.Molecular neurobiology · 2025Review
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- A SUMO-interacting motif in the guanine nucleotide exchange factor EPAC1 is required for subcellular targeting and function.bioRxiv : the preprint server for biology · 2025Article
- Epac2-mediated synaptic insertion of CaNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Non-canonical type 1 cannabinoid receptor signaling regulates night visual processing in the inner rat retina.iScience · 2024Article
- Optimized New Shengmai Powder modulation of cAMP/Rap1A signaling pathway attenuates myocardial fibrosis in heart failure.Chinese medicine · 2024Article
- Rap1 in the Context of PCSK9, Atherosclerosis, and Diabetes.Current atherosclerosis reports · 2023Review
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EPAC1, a cAMP-activated GEF for Rap GTPases, is a major transducer of cAMP signaling and a therapeutic target in cardiac diseases. The recent discovery that cAMP is compartmentalized in membrane-proximal nanodomains challenged the current model of EPAC1 activation in the cytosol. Here, we discover that anionic membranes are a major component of EPAC1 activation. We find that anionic membranes activate EPAC1 independently of cAMP, increase its affinity for cAMP by two orders of magnitude, and synergize with cAMP to yield maximal GEF activity. In the cell cytosol, where cAMP concentration is low, EPAC1 must thus be primed by membranes to bind cAMP. Examination of the cell-active chemical CE3F4 in this framework further reveals that it targets only fully activated EPAC1. Together, our findings reformulate previous concepts of cAMP signaling through EPAC proteins, with important implications for drug discovery.
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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.