title: Yorkie Regulates Neurodegeneration Through Canonical Pathway and Innate Immune Response.
abstract: Expansion of CAG repeats in certain genes has long been known to be associated with neurodegenerastion, but the quest to identity the underlying mechanisms is still on. Here, we analyzed the role of Yorkie, the coactivator of the Hippo pathway, and provide evidence to state that it is a robust genetic modifier of polyglutamine (PolyQ)-mediated neurodegeneration. Yorkie reduces the pathogenicity of inclusion bodies in the cell by activating cyclin E and bantam, rather than by preventing apoptosis through DIAP1. PolyQ aggregates inhibit Yorkie functioning at the protein, rather than the transcript level, and this is probably accomplished by the interaction between PolyQ and Yorkie. We show that PolyQ aggregates upregulate expression of antimicrobial peptides (AMPs) and Yorkie negatively regulates immune deficiency (IMD) and Toll pathways through relish and cactus, respectively, thus reducing AMPs and mitigating PolyQ affects. These studies strongly suggest a novel mechanism of suppression of PolyQ-mediated neurotoxicity by Yorkie through multiple channels.
authors.affiliation: Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Dubey
authors.affiliation: Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, 221005, India. madhu@bhu.ac.in.
authors.forename: Madhu G
authors.initials: MG
authors.lastname: Tapadia
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster; D060227:Imaginal Discs / Q000378:metabolism; D007113:Immunity, Innate / Q000502:physiology*; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila
keywords: Drosophila; Hippo; Innate immunity; Neurodegeneration; PolyQ; Yorkie