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Polyglutamine Atrophin causes autophagic neurodegeneration by repressing the fat gene

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If you have a question about this talk, please contact Shannon Tinley-Browne .

Polyglutamine Atrophin causes autophagic neurodegeneration by repressing the fat gene Large alterations in transcription accompany neurodegeneration in polyglutamine diseases. These pathologies manifest both general polyglutamine toxicity and mutant protein specific effects. Here we report that the fat tumour suppressor gene mediates neurodegeneration induced by the polyglutamine protein Atrophin. We have monitored early transcriptional alterations in a Drosophila model of Dentatorubral-pallidoluysian Atrophy and found that polyglutamine Atrophins downregulate fat. Fat protects from neurodegeneration and Atrophin toxicity through the Hippo kinase cascade. The Fat/Hippo signalling alters the autophagic flux in photoreceptor neurons, thereby affecting cell homeostasis. Our data thus provide a crucial insight into the specific mechanism of a polyglutamine disease and reveal an unexpected neuroprotective role of the Fat/Hippo pathway, linking tumour suppression and neurodegeneration.

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