β Phorbol Ester- and Diacylglycerol-Induced Augmentation of Transmitter Release Is Mediated by Munc13s and Not by PKCs
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Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming. It contains a diacylglycerol (DAG)/beta phorbol ester binding C(1) domain and is a potential target of the DAG second messenger pathway that may act in parallel with PKCs. Using genetically modified mice that express a DAG/beta phorbol ester binding-deficient Munc13-1(H567K) variant instead of the wild-type protein, we determined the relative contribution of PKCs and Munc13-1 to DAG/beta phorbol ester-dependent regulation of neurotransmitter release. We show that Munc13s are the main presynaptic DAG/beta phorbol ester receptors in hippocampal neurons. Modulation of Munc13-1 activity by second messengers via the DAG/beta phorbol ester binding C(1) domain is essential for use-dependent alterations of synaptic efficacy and survival.
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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 Rhee et al., 2002
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- Authors
- Rhee, J.-S., Betz, A., Pyott, S., Reim, K., Varoqueaux, F., Augustin, I., Hesse, D., Südhof, T. C., Takahashi, M., Rosenmund, C., & Brose, N.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- Max Planck Institute of Experimental Medicine (DE)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Rosenmund, Christian
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 108
- Issue
- 1
- Pages
- 121-133
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2032125422
- Cited by
- 500
- References
- 3
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 9 · 2023: 15 · 2022: 15 · 2021: 19 · 2020: 8 · 2019: 13 · 2018: 15 · 2017: 30 · 2016: 15 · 2015: 14 · 2014: 20 · 2013: 19 · 2012: 22
- FWCI
- 12.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 4215 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- 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, Munc13, diacylglycerol, C1 domain, protein kinase C, neurotransmitter release, synaptic vesicle priming, presynaptic modulation, hippocampal neurons, second messenger signaling, neuronal survival
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cells, Cultured, Diglycerides, Hippocampus, Molecular Sequence Data, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Phorbol Esters, Protein Kinase C, Synapses, Gene Expression, Mutagenesis, Point Mutation, Intracellular Signaling Peptides and Proteins, Mice
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