ArticleJournal of neurochemistry2013
The pre-synaptic Munc13-1 binds alcohol and modulates alcohol self-administration in Drosophila.
Article in Journal of neurochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Acute ethanol inhibits asynchronous glutamate release from mouse basolateral amygdala synapses.Neuropharmacology · 2026Article
- Single nucleotide variants inBiochemistry and biophysics reports · 2026Article
- Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025Review
- Functional Roles of UNC-13/Munc13 and UNC-18/Munc18 in Neurotransmission.Advances in neurobiology · 2023Review
- Differential Expression of Presynaptic Munc13-1 and Munc13-2 in Mouse Hippocampus Following Ethanol Drinking.Neuroscience · 2022Article
- Transcriptional analysis of the response of C. elegans to ethanol exposure.Scientific reports · 2021Article
- Probing the Diacylglycerol Binding Site of Presynaptic Munc13-1.Biochemistry · 2021Article
- (M)Unc13s in Active Zone Diversity: AFrontiers in synaptic neuroscience · 2021Review
- Effect of ethanol on Munc13-1 C1 in Membrane: A Molecular Dynamics Simulation Study.Alcoholism, clinical and experimental research · 2020Article
- MUNC13-1 heterozygosity does not alter voluntary ethanol consumption or sensitivity in mice.Alcohol (Fayetteville, N.Y.) · 2020Article
- SNARE Complex-Associated Proteins and Alcohol.Alcoholism, clinical and experimental research · 2020Review
- Munc13 Is a Molecular Target of Bryostatin 1.Biochemistry · 2019Article
- Identification of alcohol-binding site(s) in proteins using diazirine-based photoaffinity labeling and mass spectrometry.Chemical biology & drug design · 2019Article
- SNARE Complex-Associated Proteins in the Lateral Amygdala of Macaca mulatta Following Long-Term Ethanol Drinking.Alcoholism, clinical and experimental research · 2018Article
- Critical Role of Trp-588 of Presynaptic Munc13-1 for Ligand Binding and Membrane Translocation.Biochemistry · 2018Article
- Resveratrol inhibits phorbol ester-induced membrane translocation of presynaptic Munc13-1.Biochimica et biophysica acta. General subjects · 2017Article
- Genetics and genomics of alcohol responses in Drosophila.Neuropharmacology · 2017Review
- The effect of alcohol on recombinant proteins derived from mammalian adenylyl cyclase.Biochemistry and biophysics reports · 2017Article
- Strain-Dependent Effects of Acute Alcohol on Synaptic Vesicle Recycling and Post-Tetanic Potentiation in Medial Glutamate Inputs to the Mouse Basolateral Amygdala.Alcoholism, clinical and experimental research · 2017Article
- Ethanol Mediated Inhibition of Synaptic Vesicle Recycling at Amygdala Glutamate Synapses Is Dependent upon Munc13-2.Frontiers in neuroscience · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Munc13-1 is a pre-synaptic active-zone protein essential for neurotransmitter release and involved in pre-synaptic plasticity in brain. Ethanol, butanol, and octanol quenched the intrinsic fluorescence of the C1 domain of Munc13-1 with EC₅₀ s of 52 mM, 26 mM, and 0.7 mM, respectively. Photoactive azialcohols photolabeled Munc13-1 C1 exclusively at Glu-582, which was identified by mass spectrometry. Mutation of Glu-582 to alanine, leucine, and histidine reduced the alcohol binding two- to five-fold. Circular dichroism studies suggested that binding of alcohol increased the stability of the wild-type Munc13-1 compared with the mutants. If Munc13-1 plays some role in the neural effects of alcohol in vivo, changes in the activity of this protein should produce differences in the behavioral responses to ethanol. We tested this prediction with a loss-of-function mutation in the conserved Dunc-13 in Drosophila melanogaster. The Dunc-13(P84200) /+ heterozygotes have 50% wild-type levels of Dunc-13 mRNA and display a very robust increase in ethanol self-administration. This phenotype is reversed by the expression of the rat Munc13-1 protein within the Drosophila nervous system. The present studies indicate that Munc13-1 C1 has binding site(s) for alcohols and Munc13-1 activity is sufficient to restore normal self-administration to Drosophila mutants deficient in Dunc-13 activity. The pre-synaptic Mun13-1 protein is a critical regulator of synaptic vesicle fusion and may be involved in processes that lead to ethanol abuse and addiction. We studied its interaction with alcohol and identified Glu-582 as a critical residue for ethanol binding. Munc13-1 can functionally complement the Dunc13 haploinsufficient ethanol self-administration phenotype in Drosophila melanogaster, indicating that this protein participates in alcohol-induced behavioral plasticity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.