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  Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming

Varoqueaux, F., Sigler, A., Rhee, J. S., Brose, N., Enk, C., Reim, K., et al. (2002). Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming. Proceedings of the National Academy of Sciences of the United States of America, 99(13), 9037-9042. Retrieved from http://www.pnas.org/content/99/13/9037.full.pdf+html.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-F38D-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-815B-B
Genre: Journal Article

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Varoqueaux, F., Author
Sigler, A.1, Author              
Rhee, J. S.1, Author              
Brose, N., Author
Enk, C., Author
Reim, K., Author
Rosenmund, C.1, Author              
Affiliations:
1Department of Membrane Biophysics, MPI for biophysical chemistry, Max Planck Society, ou_578579              

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 Abstract: Synaptic vesicles must be primed to fusion competence before they can fuse with the plasma membrane in response to increased intracellular Ca2+ levels. The presynaptic active zone protein Munc13-1 is essential for priming of glutamatergic synaptic vesicles in hippocampal neurons. However, a small subpopulation of synapses in any given glutamatergic nerve cell as well as all gamma-aminobutyratergic (GABAergic) synapses are largely independent of Munc13-1. We show here that Munc13-2, the only Muncl 3 isoform coexpressed with Munc13-1 in hippocampus, is responsible for vesicle priming in Munc13-1 independent hippocampal synapses. Neurons lacking both Munc13-1 and Munc13- 2 show neither evoked nor spontaneous release events, yet form normal numbers of synapses with typical ultrastructural features. Thus, the two Munc13 isoforms are completely redundant in GABAergic cells whereas glutamatergic neurons form two types of synapses, one of which is solely Munc13-1 dependent and lacks Munc13-2 whereas the other type employs Munc13-2 as priming factor. We conclude that Munc13-mediated vesicle priming is not a transmitter specific phenomenon but rather a general and essential feature of multiple fast neurotransmitter systems, and that synaptogenesis during development is not dependent on synaptic secretory activity.

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Language(s): eng - English
 Dates: 2002-06-25
 Publication Status: Published in print
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 Rev. Method: Peer
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Title: Proceedings of the National Academy of Sciences of the United States of America
Source Genre: Journal
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Pages: - Volume / Issue: 99 (13) Sequence Number: - Start / End Page: 9037 - 9042 Identifier: -