ArticleScientific reports2016
Epac1 interacts with importin β1 and controls neurite outgrowth independently of cAMP and Rap1.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Selective antagonism of adenosine A2A receptor reduces hypobaric hypoxia-induced neuroinflammation by inhibiting cGAS-STING pathway.Scientific reports · 2026Article
- Tongjiang Hewei Decoction Improves Airway Hyperresponsiveness in Gastroesophageal Reflux Cough by Inhibiting ADAM33 and Epac1/Rap1 Pathway.Food science & nutrition · 2025Article
- 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
- EPAC Regulates Melanoma Growth by Stimulating mTORC1 Signaling and Loss of EPAC Signaling Dependence Correlates with Melanoma Progression.Molecular cancer research : MCR · 2022Article
- Epac2 in midbrain dopamine neurons contributes to cocaine reinforcement via enhancement of dopamine release.eLife · 2022Article
- Epac1 activation by cAMP regulates cellular SUMOylation and promotes the formation of biomolecular condensates.Science advances · 2022Article
- Exchange proteins directly activated by cyclic adenosine monophosphate inhibitor reverses mechanical allodynia via the modification of astrocytes activity in the spinal cord.Annals of translational medicine · 2021Article
- Epac: new emerging cAMP-binding protein.BMB reports · 2021Review
- Super-Resolution Imaging and Spatial Analysis of RAS on Intact Plasma Membrane Sheets.Methods in molecular biology (Clifton, N.J.) · 2021Article
- LSM12-EPAC1 defines a neuroprotective pathway that sustains the nucleocytoplasmic RAN gradient.PLoS biology · 2020Article
- Modeling Epac1 interactions with the allosteric inhibitor AM-001 by co-solvent molecular dynamics.Journal of computer-aided molecular design · 2020Article
- Review
- Mitochondrial transfer from mesenchymal stem cells to neural stem cells protects against the neurotoxic effects of cisplatin.Acta neuropathologica communications · 2018Article
- Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Exchange protein directly activated by cAMP-1 (Epac1) is a cAMP sensor that regulates multiple cellular functions including cellular migration, proliferation and differentiation. Classically, Epac1 is thought to exert its effects through binding of cAMP leading to a conformational change in Epac1 and its accumulation at the plasma membrane (PM) where it activates Rap1. In search for regulators of Epac1 activity, we show here that importin β1 (impβ1) is an Epac1 binding partner that prevents PM accumulation of Epac1. We demonstrate that in the absence of impβ1, endogenous as well as overexpressed Epac1 accumulate at the PM. Moreover, agonist-induced PM translocation of Epac1 leads to dissociation of Epac1 from impβ1. Localization of Epac1 at the PM in the absence of impβ1, requires residue R82 in its DEP domain. Notably, the PM accumulation of Epac1 in the absence of impβ1 does not require binding of cAMP to Epac1 and does not result in Rap1 activation. Functionally, PM accumulation of Epac1, an Epac1 mutant deficient in cAMP binding, or an Epac1 mutant tethered to the PM, is sufficient to inhibit neurite outgrowth. In conclusion, we uncover a cAMP-independent function of Epac1 at the PM and demonstrate that impβ1 controls subcellular localization of Epac1.
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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 Socratic graph.