Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat.
EMBO J
; 30(5): 945-58, 2011 Mar 02.
Article
em En
| MEDLINE
| ID: mdl-21278706
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Moléculas de Adesão Celular
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Epilepsias Mioclônicas Progressivas
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Proteínas de Drosophila
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Drosophila
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Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Itália