ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Phorbol esters modulate spontaneous and Ca2+-evoked transmitter release via acting on both Munc13 and protein kinase C.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 144 citations in OpenAlex.
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- Mechanisms that regulate the C1-C2B mutual inhibition control functional switch of UNC-13.eLife · 2025Article
- Distinct transmission sites within a synapse for strengthening and homeostasis.Science advances · 2025Article
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- Synapse-specific catecholaminergic modulation of neuronal glutamate release.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Roles for diacylglycerol in synaptic vesicle priming and release revealed by complete reconstitution of core protein machinery.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Rapid Quantification of First and Second Phase Insulin Secretion Dynamics using an In vitro Platform for Improving Insulin Therapy.Cell calcium · 2023Article
- Novel Roles for Diacylglycerol in Synaptic Vesicle Priming and Release Revealed by Complete Reconstitution of Core Protein Machinery.bioRxiv : the preprint server for biology · 2023Article
- L-type CaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Functional Roles of UNC-13/Munc13 and UNC-18/Munc18 in Neurotransmission.Advances in neurobiology · 2023Review
- PLC regulates spontaneous glutamate release triggered by extracellular calcium and readily releasable pool size in neocortical neurons.Frontiers in cellular neuroscience · 2023Article
- The Effect of Isosaponarin Derived from Wasabi Leaves on Glutamate Release in Rat Synaptosomes and Its Underlying Mechanism.International journal of molecular sciences · 2022Article
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- Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Munc13-1 is a CaNeuron · 2021Article
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- Endogenous neurosteroids pregnanolone and pregnanolone sulfate potentiate presynaptic glutamate release through distinct mechanisms.British journal of pharmacology · 2021Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diacylglycerol (DAG) and phorbol esters strongly potentiate transmitter release at synapses by activating protein kinase C (PKC) and members of the Munc13 family of presynaptic vesicle priming proteins. This PKC/Munc13 pathway has emerged as a crucial regulator of release probability during various forms of activity-dependent enhancement of release. Here, we investigated the relative roles of PKC and Munc13-1 in the phorbol ester potentiation of evoked and spontaneous transmitter release at the calyx of Held synapse. The phorbol ester phorbol 12,13-dibutyrate (1 microM) potentiated the frequency of miniature EPSCs, and the amplitudes of evoked EPSCs with a similar time course. Preincubating slices with the PKC blocker Ro31-82200 reduced the potentiation, mainly by affecting a late phase of the phorbol ester potentiation. The Ro31-8220-insensitive potentiation was most likely mediated by Munc13-1, because in organotypic slices of Munc13-1(H567K) knock-in mice, in which DAG binding to Munc13-1 is abolished, the potentiation of spontaneous release by phorbol ester was strongly suppressed. Using direct presynaptic depolarizations in paired recordings, we show that the phorbol ester potentiation does not go along with an increase in the number of readily releasable vesicles, despite an increase in the cumulative EPSC amplitude during 100 Hz stimulation trains. Our data indicate that activation of Munc13 and PKC both contribute to an enhancement of the fusion probability of readily releasable vesicles. Thus, docked and readily releasable vesicles are a substrate for modulation via intracellular second-messenger pathways that act via Munc13 and PKC.
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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.