Dataset Information

Glycogen synthase kinase-3/Shaggy mediates ethanol-induced excitotoxic cell death of Drosophila olfactory neurons.

ABSTRACT: It has long been known that heavy alcohol consumption leads to neuropathology and neuronal death. While the response of neurons to an ethanol insult is strongly influenced by genetic background, the underlying mechanisms are poorly understood. Here, we show that even a single intoxicating exposure to ethanol causes non-cell-autonomous apoptotic death specifically of Drosophila olfactory neurons, which is accompanied by a loss of a behavioral response to the smell of ethanol and a blackening of the third antennal segment. The Drosophila homolog of glycogen synthase kinase-3 (GSK-3)beta, Shaggy, is required for ethanol-induced apoptosis. Consistent with this requirement, the GSK-3beta inhibitor lithium protects against the neurotoxic effects of ethanol, indicating the possibility for pharmacological intervention in cases of alcohol-induced neurodegeneration. Ethanol-induced death of olfactory neurons requires both their neural activity and functional NMDA receptors. This system will allow the investigation of the genetic and molecular basis of ethanol-induced apoptosis in general and provide an understanding of the molecular role of GSK-3beta in programmed cell death.

SUBMITTER: French RL

PROVIDER: S-EPMC2791575 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Glycogen synthase kinase-3/Shaggy mediates ethanol-induced excitotoxic cell death of Drosophila olfactory neurons.

French Rachael L RL Heberlein Ulrike U

Proceedings of the National Academy of Sciences of the United States of America 20091118 49

It has long been known that heavy alcohol consumption leads to neuropathology and neuronal death. While the response of neurons to an ethanol insult is strongly influenced by genetic background, the underlying mechanisms are poorly understood. Here, we show that even a single intoxicating exposure to ethanol causes non-cell-autonomous apoptotic death specifically of Drosophila olfactory neurons, which is accompanied by a loss of a behavioral response to the smell of ethanol and a blackening of t ...[more]

PMID: 19923438

Similar Datasets

Project description:BACKGROUND: Plant Glycogen Synthase Kinase 3/ SHAGGY-like kinases (GSKs) have been implicated in numerous biological processes ranging from embryonic, flower, stomata development to stress and wound responses. They are key regulators of brassinosteroid signaling and are also involved in the cross-talk between auxin and brassinosteroid pathways. In contrast to the human genome that contains two genes, plant GSKs are encoded by a multigene family. Little is known about Liliopsida resp. Poaceae in comparison to Brassicaceae GSKs. Here, we report the identification and structural characterization of two GSK homologs named TaSK1 and TaSK2 in the hexaploid wheat genome as well as a widespread phylogenetic analysis of land plant GSKs. RESULTS: Genomic and cDNA sequence alignments as well as chromosome localization using nullisomic-tetrasomic lines provided strong evidence for three expressed gene copies located on homoeolog chromosomes for TaSK1 as well as for TaSK2. Predicted proteins displayed a clear GSK signature. In vitro kinase assays showed that TaSK1 and TaSK2 possessed kinase activity. A phylogenetic analysis of land plant GSKs indicated that TaSK1 and TaSK2 belong to clade II of plant GSKs, the Arabidopsis members of which are all involved in Brassinosteroid signaling. Based on a single ancestral gene in the last common ancestor of all land plants, paralogs were acquired and retained through paleopolyploidization events, resulting in six to eight genes in angiosperms. More recent duplication events have increased the number up to ten in some lineages. CONCLUSIONS: To account for plant diversity in terms of functionality, morphology and development, attention has to be devoted to Liliopsida resp Poaceae GSKs in addition to Arabidopsis GSKs. In this study, molecular characterization, chromosome localization, kinase activity test and phylogenetic analysis (1) clarified the homologous/paralogous versus homoeologous status of TaSK sequences, (2) pointed out their affiliation to the GSK multigene family, (3) showed a functional kinase activity, (4) allowed a classification in clade II, members of which are involved in BR signaling and (5) allowed to gain information on acquisition and retention of GSK paralogs in angiosperms in the context of whole genome duplication events. Our results provide a framework to explore Liliopsida resp Poaceae GSKs functions in development.

Project description:BackgroundGlycogen Synthase Kinase 3/SHAGGY-like kinases (GSKs) are multifunctional non-receptor ser/thr kinases. Plant GSKs are involved in hormonal signaling networks and are required for growth, development, light as well as stress responses. So far, most studies have been carried out on Arabidopsis or on other eudicotyledon GSKs. Here, we evaluated the role of TaSK1 and TaSK2, two homolog wheat (Triticum aestivum) GSKs, in brassinosteroid signaling. We explored in addition the physiological effects of brassinosteroids on wheat growth and development.ResultsA bin2-1 like gain-of-function mutation has been inserted respectively in one of the homoeologous gene copies of TaSK1 (TaSK1-A.2-1) and in one of the homoeologous gene copies of TaSK2 (TaSK2-A.2-1). Arabidopsis plants were transformed with these mutated gene copies. Severe dwarf phenotypes were obtained closely resembling those of Arabidopsis bin2-1 lines and Arabidopsis BR-deficient or BR-signaling mutants. Expression of BR downstream genes, SAUR-AC1, CPD and BAS1 was deregulated in TaSK1.2-1 and TaSK2.2-1 transgenic lines. Severe dwarf lines were partially rescued by Bikinin beforehand shown to inhibit TaSK kinase activity. This rescue was accompanied with changes in BR downstream gene expression levels. Wheat embryos and seedlings were treated with compounds interfering with BR signaling or modifying BR levels to gain insight into the role of brassinosteroids in wheat development. Embryonic axis and scutellum differentiation were impaired, and seedling growth responses were affected when embryos were treated with Epibrassinolides, Propiconazole, and Bikinin.ConclusionsIn view of our findings, TaSKs are proposed to be involved in BR signaling and to be orthologous of Arabidopsis Clade II GSK3/SHAGGY-like kinases. Observed effects of Epibrassinolide, Propiconazole and Bikinin treatments on wheat embryos and seedlings indicate a role for BR signaling in embryonic patterning and seedling growth.

Project description:BACKGROUND: GSK3 (glycogen synthase kinase 3) genes encode signal transduction proteins with roles in a variety of biological processes in eukaryotes. In contrast to the low copy numbers observed in animals, GSK3 genes have expanded into a multi-gene family in land plants (embryophytes), and have also evolved functions in diverse plant specific processes, including floral development in angiosperms. However, despite previous efforts, the phylogeny of land plant GSK3 genes is currently unclear. Here, we analyze genes from a representative sample of phylogenetically pivotal taxa, including basal angiosperms, gymnosperms, and monilophytes, to reconstruct the evolutionary history and functional diversification of the GSK3 gene family in land plants. RESULTS: Maximum Likelihood phylogenetic analyses resolve a gene tree with four major gene duplication events that coincide with the emergence of novel land plant clades. The single GSK3 gene inherited from the ancestor of land plants was first duplicated along the ancestral branch to extant vascular plants, and three subsequent duplications produced three GSK3 loci in the ancestor of euphyllophytes, four in the ancestor of seed plants, and at least five in the ancestor of angiosperms. A single gene in the Amborella trichopoda genome may be the sole survivor of a sixth GSK3 locus that originated in the ancestor of extant angiosperms. Homologs of two Arabidopsis GSK3 genes with genetically confirmed roles in floral development, AtSK11 and AtSK12, exhibit floral preferential expression in several basal angiosperms, suggesting evolutionary conservation of their floral functions. Members of other gene lineages appear to have independently evolved roles in plant reproductive tissues in individual taxa. CONCLUSIONS: Our phylogenetic analyses provide the most detailed reconstruction of GSK3 gene evolution in land plants to date and offer new insights into the origins, relationships, and functions of family members. Notably, the diversity of this "green" branch of the gene family has increased in concert with the increasing morphological and physiological complexity of land plant life forms. Expression data for seed plants indicate that the functions of GSK3 genes have also diversified during evolutionary time.

Project description:The lack of a deeper understanding of how olfactory sensory neurons (OSNs) encode odors has hindered the progress in understanding the olfactory signal processing in higher brain centers. Here we employ methods of system identification to investigate the encoding of time-varying odor stimuli and their representation for further processing in the spike domain by Drosophila OSNs. In order to apply system identification techniques, we built a novel low-turbulence odor delivery system that allowed us to deliver airborne stimuli in a precise and reproducible fashion. The system provides a 1% tolerance in stimulus reproducibility and an exact control of odor concentration and concentration gradient on a millisecond time scale. Using this novel setup, we recorded and analyzed the in-vivo response of OSNs to a wide range of time-varying odor waveforms. We report for the first time that across trials the response of OR59b OSNs is very precise and reproducible. Further, we empirically show that the response of an OSN depends not only on the concentration, but also on the rate of change of the odor concentration. Moreover, we demonstrate that a two-dimensional (2D) Encoding Manifold in a concentration-concentration gradient space provides a quantitative description of the neuron's response. We then use the white noise system identification methodology to construct one-dimensional (1D) and two-dimensional (2D) Linear-Nonlinear-Poisson (LNP) cascade models of the sensory neuron for a fixed mean odor concentration and fixed contrast. We show that in terms of predicting the intensity rate of the spike train, the 2D LNP model performs on par with the 1D LNP model, with a root mean-square error (RMSE) increase of about 5 to 10%. Surprisingly, we find that for a fixed contrast of the white noise odor waveforms, the nonlinear block of each of the two models changes with the mean input concentration. The shape of the nonlinearities of both the 1D and the 2D LNP model appears to be, for a fixed mean of the odor waveform, independent of the stimulus contrast. This suggests that white noise system identification of Or59b OSNs only depends on the first moment of the odor concentration. Finally, by comparing the 2D Encoding Manifold and the 2D LNP model, we demonstrate that the OSN identification results depend on the particular type of the employed test odor waveforms. This suggests an adaptive neural encoding model for Or59b OSNs that changes its nonlinearity in response to the odor concentration waveforms.

Dataset Information

Glycogen synthase kinase-3/Shaggy mediates ethanol-induced excitotoxic cell death of Drosophila olfactory neurons.

Publications

Glycogen synthase kinase-3/Shaggy mediates ethanol-induced excitotoxic cell death of Drosophila olfactory neurons.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets