ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Exchange Protein Directly Activated by cAMP (EPAC) Regulates Neuronal Polarization through Rap1B.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Investigating the Effects of Epac2 Activation in an In Vitro Cortical Mechanical Injury Model for Central Nervous System Repair.The European journal of neuroscience · 2025Article
- Review
- Glucose-dependent insulinotropic polypeptide (GIP) alleviates ferroptosis in aging-induced brain damage through the Epac/Rap1 signaling pathway.BMB reports · 2024Article
- Plant adenylate cyclases have come full circle.Nature plants · 2023Review
- A Role for Second Messengers in Axodendritic Neuronal Polarity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Perspectives on Mechanisms Supporting Neuronal Polarity From Small Animals to Humans.Frontiers in cell and developmental biology · 2022Review
- Epac: new emerging cAMP-binding protein.BMB reports · 2021Review
- The therapeutic potential of targeting exchange protein directly activated by cyclic adenosine 3',5'-monophosphate (Epac) for central nervous system trauma.Neural regeneration research · 2021Review
- Epac2 Elevation Reverses Inhibition by Chondroitin Sulfate ProteoglycansThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- cAMP guided his way: a life for G protein-mediated signal transduction and molecular pharmacology-tribute to Karl H. Jakobs.Naunyn-Schmiedeberg's archives of pharmacology · 2019Review
- Phosphodiesterase Inhibitors Revert Axonal Dystrophy in Friedreich's Ataxia Mouse Model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- How Rap and its GEFs control liver physiology and cancer development. C3G alterations in human hepatocarcinoma.Hepatic oncology · 2018Review
- Deletion of exchange proteins directly activated by cAMP (Epac) causes defects in hippocampal signaling in female mice.PloS one · 2018Article
- AKAP-mediated feedback control of cAMP gradients in developing hippocampal neurons.Nature chemical biology · 2017Article
- Phosphodiesterase Inhibitors as a Therapeutic Approach to Neuroprotection and Repair.International journal of molecular sciences · 2017Review
- Restoring Lost Excitability: Regenerating CNS Axons Inch Toward Electrogenicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Heterogeneity of the Axon Initial Segment in Interneurons and Pyramidal Cells of Rodent Visual Cortex.Frontiers in cellular neuroscience · 2017Article
- Epac1 interacts with importin β1 and controls neurite outgrowth independently of cAMP and Rap1.Scientific reports · 2016Article
- miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acquisition of neuronal polarity is a complex process involving cellular and molecular events. The second messenger cAMP is involved in axonal specification through activation of protein kinase A. However, an alternative cAMP-dependent mechanism involves the exchange protein directly activated by cAMP (EPAC), which also responds to physiological changes in cAMP concentration, promoting activation of the small Rap GTPases. Here, we present evidence that EPAC signaling contributes to axon specification and elongation. In primary rat hippocampal neurons, EPAC isoforms were expressed differentially during axon specification. Furthermore, 8-pCPT, an EPAC pharmacological activator, and genetic manipulations of EPAC in neurons induced supernumerary axons indicative of Rap1b activation. Moreover, 8-pCPT-treated neurons expressed ankyrin G and other markers of mature axons such as synaptophysin and axonal accumulation of vGLUT1. In contrast, pharmacological inhibition of EPAC delayed neuronal polarity. Genetic manipulations to inactivate EPAC1 using either shRNA or neurons derived from EPAC1 knock-out (KO) mice led to axon elongation and polarization defects. Interestingly, multiaxonic neurons generated by 8-pCPT treatments in wild-type neurons were not found in EPAC1 KO mice neurons. Altogether, these results propose that EPAC signaling is an alternative and complementary mechanism for cAMP-dependent axon determination. SIGNIFICANCE STATEMENT: This study identifies the guanine exchange factor responsible for Rap1b activation during neuronal polarization and provides an alternate explanation for cAMP-dependent acquisition of neuronal polarity.
Indexed as
Identifiers
What OpenQuestion holds
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.