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The Munc13 Proteins Differentially Regulate Readily Releasable Pool Dynamics and Calcium-Dependent Recovery at a Central Synapse
Open accessAbstract
The Munc13 gene family encodes molecules located at the synaptic active zone that regulate the reliability of synapses to encode information over a wide range of frequencies in response to action potentials. In the CNS, proteins of the Munc13 family are critical in regulating neurotransmitter release and synaptic plasticity. Although Munc13-1 is essential for synaptic transmission, it is paradoxical that Munc13-2 and Munc13-3 are functionally dispensable at some synapses, although their loss in other synapses leads to increases in frequency-dependent facilitation. We addressed this issue at the calyx of Held synapse, a giant glutamatergic synapse that we found to express all these Munc13 isoforms. We studied their roles in the regulation of synaptic transmission and their impact on the reliability of information transfer. Through detailed electrophysiological analyses of Munc13-2, Munc13-3, and Munc13-2-3 knock-out and wild-type mice, we report that the combined loss of Munc13-2 and Munc13-3 led to an increase in the rate of calcium-dependent recovery and a change in kinetics of release of the readily releasable pool. Furthermore, viral-mediated overexpression of a dominant-negative form of Munc13-1 at the calyx demonstrated that these effects are Munc13-1 dependent. Quantitative immunohistochemistry using Munc13–fluorescent protein knock-in mice revealed that Munc13-1 is the most highly expressed Munc13 isoform at the calyx and the only one highly colocalized with Bassoon at the active zone. Based on these data, we conclude that Munc13-2 and Munc13-3 isoforms limit the ability of Munc13-1 to regulate calcium-dependent replenishment of readily releasable pool and slow pool to fast pool conversion in central synapses.
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“and Munc13-1/2, putative markers of primed vesicles [14,42–45,60,61].”
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 [60]
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“Bassoon, a scaffold protein, is another candidate for phosphorylation, as it strongly colocalizes with Munc13-1 but not Munc13-2 at AZs [60].”
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 [60]
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Citations
Cites
Südhof, T. C. (2012) · Neuron · doi:10.1016/j.neuron.2012.06.012 · Cited by 1,062
Multiple Roles of Calcium Ions in the Regulation of Neurotransmitter Release
Neher, E., & Sakaba, T. (2008) · Neuron · doi:10.1016/j.neuron.2008.08.019 · Cited by 966
Mechanisms of Sound Localization in Mammals
Grothe, B., Pecka, M., & McAlpine, D. (2010) · Physiological Reviews · doi:10.1152/physrev.00026.2009 · Cited by 956
Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles
Augustin, I., Rosenmund, C., Südhof, T. C., & Brose, N. (1999) · Nature · doi:10.1038/22768 · Cited by 787
Schneggenburger, R., Meyer, A. C., & Neher, E. (1999) · Neuron · doi:10.1016/s0896-6273(00)80789-8 · Cited by 625
Varoqueaux, F., Sigler, A., Rhee, J.-S., Brose, N., Enk, C., Reim, K., & Rosenmund, C. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122623799 · Cited by 619
Self-citationHigh-frequency firing helps replenish the readily releasable pool of synaptic vesicles
Wang, L., & Kaczmarek, L. K. (1998) · Nature · doi:10.1038/28645 · Cited by 615
Taschenberger, H., & von Gersdorff, H. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-24-09162.2000 · Cited by 486
Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming
Betz, A., Thakur, P., Junge, H. J., Ashery, U., Rhee, J.-S., Scheuss, V., Rosenmund, C., Rettig, J., & Brose, N. (2001) · Neuron · doi:10.1016/s0896-6273(01)00272-0 · Cited by 425
Mammalian Homologues of Caenorhabditis elegans unc-13 Gene Define Novel Family of C2-domain Proteins
Brose, N., Hofmann, K., Hata, Y., & Südhof, T. C. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.42.25273 · Cited by 412
Optimizing Synaptic Architecture and Efficiency for High-Frequency Transmission
Taschenberger, H., Leão, R. M., Rowland, K. C., Spirou, G. A., & von Gersdorff, H. (2002) · Neuron · doi:10.1016/s0896-6273(02)01137-6 · Cited by 389
Calmodulin Mediates Rapid Recruitment of Fast-Releasing Synaptic Vesicles at a Calyx-Type Synapse
Sakaba, T., & Neher, E. (2001) · Neuron · doi:10.1016/s0896-6273(01)00543-8 · Cited by 363
Differential Control of Vesicle Priming and Short-Term Plasticity by Munc13 Isoforms
Rosenmund, C., Sigler, A., Augustin, I., Reim, K., Brose, N., & Rhee, J. (2002) · Neuron · doi:10.1016/s0896-6273(02)00568-8 · Cited by 346
Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain
Müller, C. S., Haupt, A., Bildl, W., Schindler, J., Knaus, H., Meissner, M., Rammner, B., Striessnig, J., Flockerzi, V., Fakler, B., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005940107 · Cited by 306
Direct Interaction of the Rat unc-13 Homologue Munc13-1 with the N Terminus of Syntaxin
Betz, A., Okamoto, M., Benseler, F., & Brose, N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.4.2520 · Cited by 304
Developmental Transformation of the Release Modality at the Calyx of Held Synapse
Fedchyshyn, M. J., & Wang, L. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0350-05.2005 · Cited by 298
Pre‐ and postnatal development of efferent connections of the cochlear nucleus in the rat
Kandler, K., & Friauf, E. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903280202 · Cited by 291
Junge, H. J., Rhee, J.-S., Jahn, O., Varoqueaux, F., Spiess, J., Waxham, M. N., Rosenmund, C., & Brose, N. (2004) · Cell · doi:10.1016/j.cell.2004.06.029 · Cited by 290
Self-citationA Munc13/RIM/Rab3 tripartite complex: from priming to plasticity?
Dulubova, I., Lou, X., Lu, J., Huryeva, I., Alam, A., Schneggenburger, R., Südhof, T. C., & Rizo, J. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600753 · Cited by 289
Sakaba, T., & Neher, E. (2003) · Nature · doi:10.1038/nature01859 · Cited by 260
The Calyx of Held Synapse: From Model Synapse to Auditory Relay
Borst, J. G. G., & van Hoeve, J. S. S. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020911-153236 · Cited by 225
Sakaba, T., & Neher, E. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00462.2001 · Cited by 216
Henriette, K. O. C. H., Hofmann, K., & Brose, N. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3490247 · Cited by 202
A General Model of Synaptic Transmission and Short-Term Plasticity
Pan, B., & Zucker, R. S. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.025 · Cited by 195
Neher, E., & Sakaba, T. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00444.2001 · Cited by 191
Hosoi, N., Sakaba, T., & Neher, E. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4122-07.2007 · Cited by 154
Forsythe, I. D., & Barnes‐Davies, M. (1993) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1993.0022 · Cited by 152
Distinct Kinetic Changes in Neurotransmitter Release After SNARE Protein Cleavage
Sakaba, T., Stein, A., Jahn, R., & Neher, E. (2005) · Science · doi:10.1126/science.1112645 · Cited by 151
Differential expression of two novel Munc13 proteins in rat brain
AUGUSTIN, I., BETZ, A., HERRMANN, C., JO, T., & BROSE, N. (1999) · Biochemical Journal · doi:10.1042/bj3370363 · Cited by 151
Wang, L., Neher, E., & Taschenberger, H. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4245-08.2008 · Cited by 142
Sakaba, T. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0182-06.2006 · Cited by 134
Young, S., & Neher, E. (2009) · Neuron · doi:10.1016/j.neuron.2009.07.028 · Cited by 134
Self-citationYang, Y., Fedchyshyn, M., Grande, G., Aitoubah, J., Tsang, C. W., Xie, H., Ackerley, C., Trimble, W., & Wang, L.-Y. (2010) · Neuron · doi:10.1016/j.neuron.2010.06.003 · Cited by 127
Augustin, I., Korte, S., Rickmann, M., Kretzschmar, H. A., Südhof, T. C., Herms, J. W., & Brose, N. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-01-00010.2001 · Cited by 125
Varoqueaux, F., Sons, M. S., Plomp, J. J., & Brose, N. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.14.5973-5984.2005 · Cited by 107
Self-citationBinding of the Munc13-1 MUN Domain to Membrane-Anchored SNARE Complexes
Guan, R. J., Dai, H., & Rizo, J. (2008) · Biochemistry · doi:10.1021/bi702345m · Cited by 106
Andrews-Zwilling, Y. S., Kawabe, H., Reim, K., Varoqueaux, F., & Brose, N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601421200 · Cited by 105
Self-citationActin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool
Lee, J. S., Ho, W., & Lee, S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114072109 · Cited by 102
Target-Dependent Feedforward Inhibition Mediated by Short-Term Synaptic Plasticity in the Cerebellum
Bao, J., Reim, K., & Sakaba, T. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0276-10.2010 · Cited by 100
Forsythe, I. D., & Barnes‐Davies, M. (1993) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1993.0021 · Cited by 98
Wang, X., Hu, B., Zieba, A., Neumann, N. G., Kasper-Sonnenberg, M., Honsbein, A., Hultqvist, G., Conze, T., Witt, W., Limbach, C., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1255-09.2009 · Cited by 96
Limbach, C., Laue, M. M., Wang, X., Hu, B., Thiede, N., Hultqvist, G., & Kilimann, M. W. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101707108 · Cited by 92
Kalla, S., Stern, M., Basu, J., Varoqueaux, F., Reim, K., Rosenmund, C., Ziv, N. E., & Brose, N. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4330-06.2006 · Cited by 88
Self-citationLi, W., Ma, C., Guan, R. J., Xu, Y., Tomchick, D. R., & Rizo, J. (2011) · Structure · doi:10.1016/j.str.2011.07.012 · Cited by 86
On the classification of pathways in the auditory midbrain, thalamus, and cortex
Lee, C. C., & Sherman, S. M. (2010) · Hearing Research · doi:10.1016/j.heares.2010.12.012 · Cited by 80
Rodríguez-Castañeda, F., Maestre-Martínez, M., Coudevylle, N., Dimova, K. P., Junge, H. J., Lipstein, N., Lee, D., Becker, S., Brose, N., Jahn, O., et al. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.373 · Cited by 77
Estimating Transmitter Release Rates from Postsynaptic Current Fluctuations
Neher, E., & Sakaba, T. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-24-09638.2001 · Cited by 67
Munc13-Independent Vesicle Priming at Mouse Photoreceptor Ribbon Synapses
Cooper, B. H., Hemmerlein, M., Ammermüller, J., Imig, C., Reim, K., Lipstein, N., Kalla, S., Kawabe, H., Brose, N., Brandstätter, J. H., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4240-11.2012 · Cited by 63
Self-citationLee, J. S., Ho, W., & Lee, S. (2010) · The Journal of General Physiology · doi:10.1085/jgp.201010437 · Cited by 61
Pilpel, N., Landeck, N., Klugmann, M., Seeburg, P. H., & Schwarz, M. K. (2009) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2009.05.020 · Cited by 61
Proteomics analysis of immuno-precipitated synaptic protein complexes
Klemmer, P., Smit, A. B., & Li, K. W. (2008) · Journal of Proteomics · doi:10.1016/j.jprot.2008.10.005 · Cited by 54
Vesicle Priming and Recruitment by ubMunc13-2 Are Differentially Regulated by Calcium and Calmodulin
Zikich, D., Mezer, A., Varoqueaux, F., Sheinin, A., Junge, H. J., Nachliel, E., Melamed, R., Brose, N., Gutman, M., & Ashery, U. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5096-07.2008 · Cited by 51
Self-citationMunc13-2 Differentially Affects Hippocampal Synaptic Transmission and Plasticity
Breustedt, J., Gundlfinger, A., Varoqueaux, F., Reim, K., Brose, N., & Schmitz, D. (2010) · Cerebral Cortex · doi:10.1093/cercor/bhp170 · Cited by 51
Self-citationMontesinos, M. S., Chen, Z., & Young, S. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00713.2011 · Cited by 21
Self-citation1H, 13C and 15N resonance assignments of the Calmodulin-Munc13-1 peptide complex
Rodríguez-Castañeda, F., Coudevylle, N., Becker, S., Brose, N., Carlomagno, T., & Griesinger, C. (2009) · Biomolecular NMR Assignments · doi:10.1007/s12104-009-9204-2 · Cited by 4
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Metadata
- Authors
- Chen, Z., Cooper, B., Kalla, S., Varoqueaux, F., & Young, S. M.
- Affiliations
- Max Planck Florida Institute for Neuroscience (US)
- Max Planck Institute of Experimental Medicine (DE)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-05-08
- Volume
- 33
- Issue
- 19
- Pages
- 8336-8351
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6619620
- OpenAlex
- W2079607057
- Cited by
- 102
- References
- 55
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 10 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 12 · 2017: 11 · 2016: 5 · 2015: 10 · 2014: 7 · 2013: 3
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- IRIS (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Munc13, Munc13-1, readily releasable pool, calyx of Held, synaptic transmission, synaptic reliability, glutamatergic synapses, active zone, bassoon, knockout mice
- MeSH terms
- Age Factors, Analysis of Variance, Animals, Animals, Newborn, Brain Stem, Calcium, Electric Stimulation, Female, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Synaptic Transmission, Synapses, Mice, Knockout, Patch-Clamp Techniques, Gene Expression Regulation, Developmental, Excitatory Postsynaptic Potentials, Intracellular Signaling Peptides and Proteins, Green Fluorescent Proteins, Vesicular Glutamate Transport Protein 1, Mice, In Vitro Techniques
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