Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat.
Copyright policy )Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat.
Large alterations in transcription accompany neurodegeneration in polyglutamine (polyQ) diseases. These pathologies manifest both general polyQ toxicity and mutant protein-specific effects. In this study, we report that the fat tumour suppressor gene mediates neurodegeneration induced by the polyQ protein Atrophin. We have monitored early transcriptional alterations in a Drosophila model of Dentatorubral-pallidoluysian Atrophy and found that polyQ Atrophins downregulate fat. Fat protects from neurodegeneration and Atrophin toxicity through the Hippo kinase cascade. Fat/Hippo signalling does not provoke neurodegeneration by stimulating overgrowth; rather, it alters the autophagic flux in photoreceptor neurons, thereby affecting cell homeostasis. Our data thus provide a crucial insight into the specific mechanism of a polyQ disease and reveal an unexpected neuroprotective role of the Fat/Hippo pathway.
- King's College London United Kingdom
- University of Trieste Italy
- Kings College London, University of London United Kingdom
570, autophagy, Transcription, Genetic, Immunology and Microbiology (all), Hippo pathway, Immunoenzyme Technique, 610, Nerve Tissue Proteins, Immunoenzyme Techniques, fat, Autophagy, Animals, Drosophila Proteins, Atrophin; autophagy; fat; Hippo pathway; neurodegeneration; Animals; Autophagy; Cell Adhesion Molecules; Disease Models, Animal; Drosophila; Drosophila Proteins; Immunoenzyme Techniques; Myoclonic Epilepsies, Progressive; Nerve Degeneration; Nerve Tissue Proteins; Neurons; Peptides; Signal Transduction; Transcription, Genetic; Neuroscience (all); Molecular Biology; Biochemistry, Genetics and Molecular Biology (all); Immunology and Microbiology (all), Molecular Biology, Neurons, Neuroscience (all), Biochemistry, Genetics and Molecular Biology (all), Animal, neurodegeneration, Neuron, Myoclonic Epilepsies, Progressive, Disease Models, Animal, Cell Adhesion Molecule, Nerve Tissue Protein, Peptide, Nerve Degeneration, Drosophila Protein, Drosophila, Peptides, Cell Adhesion Molecules, Atrophin, Signal Transduction
570, autophagy, Transcription, Genetic, Immunology and Microbiology (all), Hippo pathway, Immunoenzyme Technique, 610, Nerve Tissue Proteins, Immunoenzyme Techniques, fat, Autophagy, Animals, Drosophila Proteins, Atrophin; autophagy; fat; Hippo pathway; neurodegeneration; Animals; Autophagy; Cell Adhesion Molecules; Disease Models, Animal; Drosophila; Drosophila Proteins; Immunoenzyme Techniques; Myoclonic Epilepsies, Progressive; Nerve Degeneration; Nerve Tissue Proteins; Neurons; Peptides; Signal Transduction; Transcription, Genetic; Neuroscience (all); Molecular Biology; Biochemistry, Genetics and Molecular Biology (all); Immunology and Microbiology (all), Molecular Biology, Neurons, Neuroscience (all), Biochemistry, Genetics and Molecular Biology (all), Animal, neurodegeneration, Neuron, Myoclonic Epilepsies, Progressive, Disease Models, Animal, Cell Adhesion Molecule, Nerve Tissue Protein, Peptide, Nerve Degeneration, Drosophila Protein, Drosophila, Peptides, Cell Adhesion Molecules, Atrophin, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).68 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!