ArticlePloS one2012
DlgS97/SAP97, a neuronal isoform of discs large, regulates ethanol tolerance.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Memory-like states created by the first ethanol experience are encoded into the Drosophila mushroom body learning and memory circuitry in an ethanol-specific manner.PLoS genetics · 2025Article
- A Brief Overview of Ethanol Tolerance and Its Potential Association with Circadian Rhythm inInternational journal of molecular sciences · 2024Review
- Synaptic Mechanisms of Ethanol Tolerance and Neuroplasticity: Insights from Invertebrate Models.International journal of molecular sciences · 2024Review
- Review
- Large analysis of genetic manipulations reveals an inverse correlation between initial alcohol resistance and rapid tolerance phenotypes.Genes, brain, and behavior · 2024Article
- Large genetic analysis of alcohol resistance and tolerance reveals an inverse correlation and suggests 'true' tolerance mutants.bioRxiv : the preprint server for biology · 2023Article
- Molecular Profiling of VGluT1 AND VGluT2 Ventral Subiculum to Nucleus Accumbens Shell Projections.Neurochemical research · 2023Article
- Dlg Is Required for Short-Term Memory and Interacts with NMDAR in theInternational journal of molecular sciences · 2022Article
- Repeated ethanol intoxications of Drosophila melanogaster adults increases the resistance to ethanol of their progeny.Alcoholism, clinical and experimental research · 2021Article
- Receptors and Channels Associated with Alcohol Use: Contributions fromNeuroscience insights · 2021Review
- F654A and K558Q Mutations in NMDA Receptor 1 Affect Ethanol-Induced Behaviors in Drosophila.Alcoholism, clinical and experimental research · 2019Article
- Insights from intoxicated Drosophila.Alcohol (Fayetteville, N.Y.) · 2019Review
- Alignment of the transcriptome with individual variation in animals selectively bred for High Drinking-In-the-Dark (HDID).Alcohol (Fayetteville, N.Y.) · 2017Article
- Effects of selection for ethanol preference on gene expression in the nucleus accumbens of HS-CC mice.Genes, brain, and behavior · 2017Article
- Polymorphisms in early neurodevelopmental genes affect natural variation in alcohol sensitivity in adult drosophila.BMC genomics · 2015Article
- Drosophila and Caenorhabditis elegans as Discovery Platforms for Genes Involved in Human Alcohol Use Disorder.Alcoholism, clinical and experimental research · 2015Review
- Is alcoholism learned? Insights from the fruit fly.Current opinion in neurobiology · 2013Article
- Immediate-early alcohol-responsive miRNA expression in Drosophila.Journal of neurogeneticsArticle
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
From a genetic screen for Drosophila melanogaster mutants with altered ethanol tolerance, we identified intolerant (intol), a novel allele of discs large 1 (dlg1). Dlg1 encodes Discs Large 1, a MAGUK (Membrane Associated Guanylate Kinase) family member that is the highly conserved homolog of mammalian PSD-95 and SAP97. The intol mutation disrupted specifically the expression of DlgS97, a SAP97 homolog, and one of two major protein isoforms encoded by dlg1 via alternative splicing. Expression of the major isoform, DlgA, a PSD-95 homolog, appeared unaffected. Ethanol tolerance in the intol mutant could be partially restored by transgenic expression of DlgS97, but not DlgA, in specific neurons of the fly's brain. Based on co-immunoprecipitation, DlgS97 forms a complex with N-methyl-D-aspartate (NMDA) receptors, a known target of ethanol. Consistent with these observations, flies expressing reduced levels of the essential NMDA receptor subunit dNR1 also showed reduced ethanol tolerance, as did mutants in the gene calcium/calmodulin-dependent protein kinase (caki), encoding the fly homolog of mammalian CASK, a known binding partner of DlgS97. Lastly, mice in which SAP97, the mammalian homolog of DlgS97, was conditionally deleted in adults failed to develop rapid tolerance to ethanol's sedative/hypnotic effects. We propose that DlgS97/SAP97 plays an important and conserved role in the development of tolerance to ethanol via NMDA receptor-mediated synaptic plasticity.
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Registered trials
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.