Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles
- PMID: 10440375
- DOI: 10.1038/22768
Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles
Abstract
Neurotransmitter release at synapses between nerve cells is mediated by calcium-triggered exocytotic fusion of synaptic vesicles. Before fusion, vesicles dock at the presynaptic release site where they mature to a fusion-competent state. Here we identify Munc13-1, a brain-specific presynaptic phorbol ester receptor, as an essential protein for synaptic vesicle maturation. We show that glutamatergic hippocampal neurons from mice lacking Munc13-1 form ultrastructurally normal synapses whose synaptic-vesicle cycle is arrested at the maturation step. Transmitter release from mutant synapses cannot be triggered by action potentials, calcium-ionophores or hypertonic sucrose solution. In contrast, release evoked by alpha-latrotoxin is indistinguishable from wild-type controls, indicating that the toxin can bypass Munc13-1-mediated vesicle maturation. A small subpopulation of synapses of any given glutamatergic neuron as well as all synapses of GABA (gamma-aminobutyric acid)-containing neurons are unaffected by Munc13-1 loss, demonstrating the existence of multiple and transmitter-specific synaptic vesicle maturation processes in synapses.
Similar articles
-
Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming.Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):9037-42. doi: 10.1073/pnas.122623799. Epub 2002 Jun 17. Proc Natl Acad Sci U S A. 2002. PMID: 12070347 Free PMC article.
-
The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion.Nature. 1997 Jun 19;387(6635):810-4. doi: 10.1038/42954. Nature. 1997. PMID: 9194562
-
A common molecular basis for membrane docking and functional priming of synaptic vesicles.Eur J Neurosci. 2009 Jul;30(1):49-56. doi: 10.1111/j.1460-9568.2009.06811.x. Epub 2009 Jun 25. Eur J Neurosci. 2009. PMID: 19558619
-
The sequence of events that underlie quantal transmission at central glutamatergic synapses.Nat Rev Neurosci. 2007 Aug;8(8):597-609. doi: 10.1038/nrn2191. Nat Rev Neurosci. 2007. PMID: 17637801 Review.
-
Impaired glutamatergic synaptic transmission in the PKU brain.Mol Genet Metab. 2005 Dec;86 Suppl 1:S34-42. doi: 10.1016/j.ymgme.2005.06.014. Epub 2005 Sep 8. Mol Genet Metab. 2005. PMID: 16153867 Review.
Cited by
-
Enlightening molecular mechanisms through study of protein interactions.J Mol Cell Biol. 2012 Oct;4(5):270-83. doi: 10.1093/jmcb/mjs036. Epub 2012 Jun 26. J Mol Cell Biol. 2012. PMID: 22735643 Free PMC article. Review.
-
Molecular machines in the synapse: overlapping protein sets control distinct steps in neurosecretion.PLoS Comput Biol. 2012;8(4):e1002450. doi: 10.1371/journal.pcbi.1002450. Epub 2012 Apr 5. PLoS Comput Biol. 2012. PMID: 22496630 Free PMC article.
-
ELKS controls the pool of readily releasable vesicles at excitatory synapses through its N-terminal coiled-coil domains.Elife. 2016 Jun 2;5:e14862. doi: 10.7554/eLife.14862. Elife. 2016. PMID: 27253063 Free PMC article.
-
Lighting a path: genetic studies pinpoint neurodevelopmental mechanisms in autism and related disorders.Dialogues Clin Neurosci. 2012 Sep;14(3):239-52. Dialogues Clin Neurosci. 2012. PMID: 23226950 Free PMC article. Review.
-
Endogenous neurosteroids pregnanolone and pregnanolone sulfate potentiate presynaptic glutamate release through distinct mechanisms.Br J Pharmacol. 2021 Oct;178(19):3888-3904. doi: 10.1111/bph.15529. Epub 2021 Jun 22. Br J Pharmacol. 2021. PMID: 33988248 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
