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Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat
Author(s) -
Napoletano Francesco,
Occhi Simona,
Calamita Piera,
Volpi Vera,
Blanc Eric,
Charroux Bernard,
Royet Julien,
Fanto Manolis
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.1
Subject(s) - biology , neurodegeneration , drosophila (subgenus) , microbiology and biotechnology , genetics , medicine , disease , gene
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.