Differential expression of two novel Munc13 proteins in rat brain
Open accessAbstract
Munc13-1, a mammalian homologue of Caenorhabditis elegans unc-13p, is a presynaptic phorbol ester receptor that enhances neurotransmitter release. In the present study we analysed the regional, cellular and subcellular expression patterns in rat of two novel Munc13 proteins, Munc13-2 and Munc13-3. We demonstrate by hybridization in situ that Munc13-1 mRNA is expressed throughout the brain, whereas Munc13-2 mRNA is preferentially present in rostral brain regions, and Munc13-3 mRNA in caudal areas. In an analysis of subcellular brain fractions with isoform-specific antibodies, we show that the novel Munc13 proteins are enriched in synapses. Immunocytochemical examination of rat cerebellar sections indicates that Munc13-3, like Munc13-1, is concentrated in presynaptic terminals. Our results characterize Munc13 proteins as a family of neuron-specific, synaptic molecules that bind to syntaxin, an essential mediator of neurotransmitter release. Munc13-2 and Munc13-3 are expressed in a complementary fashion and might act in concert with Munc13-1 to modulate neurotransmitter release.
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Forskolin slightly reduces the distance between CaV2.1 Ca2+ channels and Munc13-1.
“Furthermore, we discovered that forskolin slightly reduced the distance between CaV2.1 (P/Q-type) Ca2+ channels and Munc13-1, an essential vesicle priming protein and putative marker of primed vesicles [14,40–45].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [40]
The forskolin-related distance change is presented as the citing authors’ own discovery, not as a finding attributed to this source. The Introduction (page unavailable) says Munc13-1 is localized to presynaptic release sites and is thought to function in vesicle recruitment, docking or priming. It does not establish that Munc13-1 is essential for priming or a marker of primed vesicles. (LLM, conf=0.82)
Experimental — accuracy not yet measuredbMunc13-2 is the second-most abundant isoform expressed at mossy fiber bouton synapses.
“After Munc13-1, the second-most abundant isoform expressed at MFB synapses is bMunc13-2 [40,42,77].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [40]
The Discussion describes Munc13-1 as the most abundant isoform, and the protein-characterization section reports Munc13-2 in synaptic membrane fractions. Neither section identifies bMunc13-2 or ranks isoform abundance at mossy fiber bouton synapses; the localization section measures hippocampal mRNA by region, not protein abundance at those synapses. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredForskolin changes only the localization of Munc13-1 but not bMunc13-2, which lacks C2A domain and is thought to prime vesicles independently of RIM.
“In this context, it is interesting that forskolin changes only the localization of Munc13-1 but not bMunc13-2, which lacks C2A domain and is thought to prime vesicles independently of RIM [40,96].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [40]
The Introduction describes Munc13-1 translocation in response to diacylglycerol or phorbol ester, and the characterization section reports baseline localization of Munc13 isoforms. Neither addresses a forskolin-induced change, whether bMunc13-2 lacks C2A, or RIM-independent priming; searches for forskolin, C2A, and RIM found no passage establishing those points. Page numbers were not available in our copy. (LLM, conf=0.73)
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- Authors
- AUGUSTIN, I., BETZ, A., HERRMANN, C., JO, T., & BROSE, N.
- Affiliations
- Max Planck Institute of Experimental Medicine (DE)
- Max Planck Institute for Biophysical Chemistry (DE)
- Corresponding author
- AUGUSTIN, Iris
- BETZ, Andrea
- BROSE, Nils
- ORCID
- BROSE, Nils
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1999-01-25
- Volume
- 337
- Issue
- 3
- Pages
- 363-371
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1219986
- OpenAlex
- W2046553750
- Cited by
- 151
- References
- 29
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 8 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 6 · 2017: 9 · 2016: 3 · 2015: 4 · 2014: 5 · 2013: 5 · 2012: 5
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB406/A1)
- 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 › Extracellular vesicles in disease
- Keywords
- Munc13-1, presynaptic proteins, neurotransmitter release, syntaxin, presynaptic terminals, cerebellum, brain regional expression, subcellular localization, synapses, rat brain
- MeSH terms
- Amino Acid Sequence, Animals, Brain, Male, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Organ Specificity, RNA, Messenger, Subcellular Fractions, Rats, Wistar, In Situ Hybridization, Intracellular Signaling Peptides and Proteins, Qa-SNARE Proteins, Mice, Rats
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