Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat
Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat
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DOI：
10.1038/emboj.2011.1
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发表时间：
2011-03-02
期刊：
影响因子：
11.4
通讯作者：
Fanto, Manolis
中科院分区：
文献类型：
--
作者：
Napoletano, Francesco;Occhi, Simona;Fanto, Manolis
多聚谷氨酰胺（polyQ）疾病中的神经变性伴随着转录的巨大改变。这些病理表现出一般的 PolyQ 毒性和突变蛋白特异性效应。在这项研究中，我们报道了脂肪肿瘤抑制基因介导由polyQ蛋白Atropin诱导的神经变性。我们监测了齿状红核-苍白球路易体萎缩果蝇模型的早期转录改变，发现 PolyQ 萎缩蛋白下调脂肪。脂肪通过河马激酶级联反应防止神经变性和萎缩蛋白毒性。 Fat/Hippo 信号传导不会通过刺激过度生长而引发神经变性；相反，它改变了感光神经元的自噬通量，从而影响细胞稳态。因此，我们的数据为 PolyQ 疾病的具体机制提供了重要的见解，并揭示了 Fat/Hippo 通路意想不到的神经保护作用。 EMBO 杂志 (2011) 30, 945-958。 doi：10.1038/emboj.2011.1； 2011 年 1 月 28 日在线发布
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