Journal article
The Munc13 Proteins Differentially Regulate Readily Releasable Pool Dynamics and Calcium-Dependent Recovery at a Central Synapse
The Journal of neuroscience, Vol.33(19), pp.8336-8351
05/08/2013
DOI: 10.1523/JNEUROSCI.5128-12.2013
PMCID: PMC6619620
PMID: 23658173
Abstract
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.
Details
- Title: Subtitle
- The Munc13 Proteins Differentially Regulate Readily Releasable Pool Dynamics and Calcium-Dependent Recovery at a Central Synapse
- Creators
- Zuxin Chen - School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, ChinaBenjamin Cooper - Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, D-37075 Goettingen, GermanyStefan Kalla - Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, D-37075 Goettingen, GermanyFrederique Varoqueaux - Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, D-37075 Goettingen, GermanySamuel M Young - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute, Jupiter, Florida 33458
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.33(19), pp.8336-8351
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.5128-12.2013
- PMID
- 23658173
- PMCID
- PMC6619620
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 05/08/2013
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
- Record Identifier
- 9984025462702771
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