Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat

Francesco Napoletano; Simona Occhi; Piera Calamita; Vera Volpi; Eric Blanc; Bernard Charroux; Julien Royet; Manolis Fanto

doi:10.1038/emboj.2011.1

Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat

Francesco Napoletano, Simona Occhi, Piera Calamita, Vera Volpi, Eric Blanc, Bernard Charroux, Julien Royet, Manolis Fanto

Developmental Neurobiology

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59 Citations (Scopus)

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. The EMBO Journal (2011) 30, 945-958. doi: 10.1038/emboj.2011.1; Published online 28 January 2011

Original language	English
Pages (from-to)	945 - 958
Number of pages	14
Journal	EMBO Journal
Volume	30
Issue number	5
DOIs	https://doi.org/10.1038/emboj.2011.1
Publication status	Published - 2 Mar 2011

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title = "Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat",

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. The EMBO Journal (2011) 30, 945-958. doi: 10.1038/emboj.2011.1; Published online 28 January 2011",

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T1 - Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat

AU - Napoletano, Francesco

AU - Occhi, Simona

AU - Calamita, Piera

AU - Volpi, Vera

AU - Blanc, Eric

AU - Charroux, Bernard

AU - Royet, Julien

AU - Fanto, Manolis

PY - 2011/3/2

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N2 - 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. The EMBO Journal (2011) 30, 945-958. doi: 10.1038/emboj.2011.1; Published online 28 January 2011

AB - 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. The EMBO Journal (2011) 30, 945-958. doi: 10.1038/emboj.2011.1; Published online 28 January 2011

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ER -

Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat

Abstract

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