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ID: 16490.0, MPI für biophysikalische Chemie / Abteilungsunabhängige Arbeitsgruppen
Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming
Authors:Varoqueaux, F.; Sigler, A.; Rhee, J. S.; Brose, N.; Enk, C.; Reim, K.; Rosenmund, C.
Language:English
Date of Publication (YYYY-MM-DD):2002-06-25
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America
Volume:99
Issue / Number:13
Start Page:9037
End Page:9042
Review Status:Peer-review
Audience:Not Specified
Abstract / Description: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.
Comment of the Author/Creator:Date: 2002, JUN 25
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/AG Christian Rosenmund
External Affiliations:Max Planck Inst Expt Med, Dept Mol Neurobiol, D-37075; Gottingen, Germany;
Identifiers:URL:http://www.pnas.org/content/99/13/9037.full.pdf+ht...
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