ArticleThe Journal of biological chemistry2013
β-Adrenergic receptors activate exchange protein directly activated by cAMP (Epac), translocate Munc13-1, and enhance the Rab3A-RIM1α interaction to potentiate glutamate release at cerebrocortical nerve terminals.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Coordinated regulation of timing and strength of synaptic outputs by adrenergic receptors through control of action potentials in Purkinje cells.Frontiers in cellular neuroscience · 2025Article
- Article
- Non-canonical type 1 cannabinoid receptor signaling regulates night visual processing in the inner rat retina.iScience · 2024Article
- Fully-primed slowly-recovering vesicles mediate presynaptic LTP at neocortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- cAMP-EPAC-PKCε-RIM1α signaling regulates presynaptic long-term potentiation and motor learning.eLife · 2023Article
- The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome.Molecular autism · 2023Article
- Epac2 in midbrain dopamine neurons contributes to cocaine reinforcement via enhancement of dopamine release.eLife · 2022Article
- Epac: new emerging cAMP-binding protein.BMB reports · 2021Review
- β-Adrenergic Receptors/Epac Signaling Increases the Size of the Readily Releasable Pool of Synaptic Vesicles Required for Parallel Fiber LTP.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Ascending noradrenergic excitation from the locus coeruleus to the anterior cingulate cortex.Molecular brain · 2020Article
- EPAC2: A new and promising protein for glioma pathogenesis and therapy.Oncology reviews · 2020Article
- AMP-activated protein kinase slows D2 dopamine autoreceptor desensitization in substantia nigra neurons.Neuropharmacology · 2019Article
- Emotional arousal amplifies competitions across goal-relevant representation: A neurocomputational framework.Cognition · 2019Article
- Suppression of osteoclastogenesis via α2-adrenergic receptors.Biomedical reports · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Decreased autophagy induced by βCell death & disease · 2018Article
- Bidirectional modulation of glutamatergic synaptic transmission by metabotropic glutamate type 7 receptors at Schaffer collateral-CA1 hippocampal synapses.The Journal of physiology · 2018Article
- Arousal increases neural gain via the locus coeruleus-norepinephrine system in younger adults but not in older adults.Nature human behaviour · 2018Article
- βFrontiers in pharmacology · 2018Article
- Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adenylyl cyclase activator forskolin facilitates synaptic transmission presynaptically via cAMP-dependent protein kinase (PKA). In addition, cAMP also increases glutamate release via PKA-independent mechanisms, although the downstream presynaptic targets remain largely unknown. Here, we describe the isolation of a PKA-independent component of glutamate release in cerebrocortical nerve terminals after blocking Na(+) channels with tetrodotoxin. We found that 8-pCPT-2'-O-Me-cAMP, a specific activator of the exchange protein directly activated by cAMP (Epac), mimicked and occluded forskolin-induced potentiation of glutamate release. This Epac-mediated increase in glutamate release was dependent on phospholipase C, and it increased the hydrolysis of phosphatidylinositol 4,5-bisphosphate. Moreover, the potentiation of glutamate release by Epac was independent of protein kinase C, although it was attenuated by the diacylglycerol-binding site antagonist calphostin C. Epac activation translocated the active zone protein Munc13-1 from soluble to particulate fractions; it increased the association between Rab3A and RIM1α and redistributed synaptic vesicles closer to the presynaptic membrane. Furthermore, these responses were mimicked by the β-adrenergic receptor (βAR) agonist isoproterenol, consistent with the immunoelectron microscopy and immunocytochemical data demonstrating presynaptic expression of βARs in a subset of glutamatergic synapses in the cerebral cortex. Based on these findings, we conclude that βARs couple to a cAMP/Epac/PLC/Munc13/Rab3/RIM-dependent pathway to enhance glutamate release at cerebrocortical nerve terminals.
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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.