Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release
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Munc13-1, a mammalian homolog of C. elegans unc-13p, is thought to be involved in the regulation of synaptic transmission. We now demonstrate that Munc13-1 is a presynaptic high-affinity phorbol ester and diacylglycerol receptor with ligand affinities similar to those of protein kinase C. Munc13-1 associates with the plasma membrane in response to phorbol ester binding and acts as a phorbol ester-dependent enhancer of transmitter release when overexpressed presynaptically in the Xenopus neuromuscular junction. These observations establish Munc13-1 as a novel presynaptic target of the diacylglycerol second messenger pathway that acts in parallel with protein kinase C to regulate neurotransmitter secretion.
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The central C1 domain of Munc13 binds to diacyl-glycerol as an endogenous ligand and to phorbol esters as a pharmacological activator, and its activation dramatically activates neurotransmitter release.
“The central C1 domain of Munc13’s binds to diacyl-glycerol as an endogenous ligand and to phorbol esters as a pharmacological activator (Betz et al., 1998), and its activation also dramatically activates neurotransmitter release (Figure 5D; Rhee et al., 2002).”
From The Presynaptic Active Zone (2012) · cites this paper as Betz et al., 1998
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References 55 · Cited by 425
- Authors
- Betz, A., Ashery, U., Rickmann, M., Augustin, I., Neher, E., Südhof, T. C., Rettig, J., & Brose, N.
- Affiliations
- Max Planck Institute of Experimental Medicine (DE)
- Max Planck Institute for Biophysical Chemistry (DE)
- University of Göttingen (DE)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Brose, Nils
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1998-07
- Volume
- 21
- Issue
- 1
- Pages
- 123-136
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2018461674
- Cited by
- 425
- References
- 55
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 5 · 2023: 12 · 2022: 13 · 2021: 15 · 2020: 7 · 2019: 6 · 2018: 11 · 2017: 24 · 2016: 11 · 2015: 10 · 2014: 12 · 2013: 15 · 2012: 12
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Munc13-1, phorbol ester receptor, diacylglycerol, presynaptic neurotransmitter release, protein kinase C, synaptic transmission, neuromuscular junction, second messenger signaling, plasma membrane binding
- MeSH terms
- Amino Acid Sequence, Animals, Biological Transport, Brain, Carrier Proteins, Cell Line, Female, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Synaptic Transmission, Neuromuscular Junction, Phorbol Esters, Protein Kinase C, Receptors, Drug, Tissue Distribution, Xenopus, Rats, Sprague-Dawley, Presynaptic Terminals, Neurotransmitter Agents, Caenorhabditis elegans Proteins, Rats
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