Studying polyglutamine diseases in Drosophila

Xu, Zhen; Tito, Antonio; Rui, Yanning; Zhang, Sheng

doi:10.1016/j.expneurol.2015.08.002

Cited by 37 publications

(30 citation statements)

References 288 publications

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“…Eye-specific expression of Huntingtin-polyQ polypeptides (HTT.Q93) results in neuronal degeneration reflected by depigmentation of the adult eye (Figure 6F,I, Supplemental Table 2) as previously shown (Xu et al, 2015). This depigmentation phenotype is suppressed by knockdown of the Nil phosphatase (Figure 6G,J, Supplemental Table 2) but only marginally altered by overexpression of PPM1B, the human homolog of Nil, (Figure 6H,K, Supplemental Table 2).…”

Section: Phosphorylation Of Acn Serine 437 In Nil 1 Animal Elevates Basal Autophagysupporting

confidence: 70%

A phospho-switch at Acinus-Serine⁴³⁷ controls autophagic responses to Cadmium exposure and neurodegenerative stress

Nandi

Zaidi

Tracy

et al. 2021

Preprint

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Neuronal health depends on quality control functions of autophagy, but mechanisms regulating neuronal autophagy are poorly understood. Previously, we showed that in Drosophila starvation-independent quality control autophagy is regulated by Acinus and the Cdk5-dependent phosphorylation of its serine437 (Nandi et al., 2017). Here, we identify the phosphatase that counterbalances this activity and provides for the dynamic nature of Acinus-S437 phosphorylation. A genetic screen identified six phosphatases that genetically interacted with an Acinus gain-of-function model. Among these, loss of function of only one, the PPM-type phosphatase Nil (CG6036), enhanced pS437-Acinus levels. Cdk5-dependent phosphorylation of Acinus serine437 in nil1 animals elevates neuronal autophagy and reduces the accumulation of polyQ proteins in a Drosophila Huntington's disease model. Consistent with previous findings that Cd2+ inhibits PPM-type phosphatases, Cd2+-exposure elevated Acinus-serine437 phosphorylation which was necessary for increased neuronal autophagy and protection against Cd2+-induced cytotoxicity. Together, our data establish the Acinus-S437 phospho-switch as critical integrator of multiple stress signals regulating neuronal autophagy.

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Section: Phosphorylation Of Acn Serine 437 In Nil 1 Animal Elevates Basal Autophagysupporting

confidence: 70%

A phospho-switch at Acinus-Serine⁴³⁷ controls autophagic responses to Cadmium exposure and neurodegenerative stress

Nandi

Zaidi

Tracy

et al. 2021

Preprint

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“…Then, the publication of the first annotated version of Drosophila genomic sequence (Myers et al, 2000 ) confirmed that many human genes involved in all kinds of human diseases had an ortholog counterpart in the fly (Reiter et al, 2001 ). Moreover, genetic manipulation of those genes has successfully led to molecular, biochemical, tissue and behavioral defects that mirror the human conditions (Botella et al, 2009 ; Bouleau and Tricoire, 2015 ; Casci and Pandey, 2015 ; Xu et al, 2015 ). A remarkable example is the discovery of the molecular basis of behavior by characterization of genes controlling circadian rhythm and the biological clock (Konopka and Benzer, 1971 ).…”

Section: Introductionmentioning

confidence: 99%

Copper and Zinc Homeostasis: Lessons from Drosophila melanogaster

Navarro

Schneuwly

2017

Front. Genet.

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Maintenance of metal homeostasis is crucial for many different enzymatic activities and in turn for cell function and survival. In addition, cells display detoxification and protective mechanisms against toxic accumulation of metals. Perturbation of any of these processes normally leads to cellular dysfunction and finally to cell death. In the last years, loss of metal regulation has been described as a common pathological feature in many human neurodegenerative diseases. However, in most cases, it is still a matter of debate whether such dyshomeostasis is a primary or a secondary downstream defect. In this review, we will summarize and critically evaluate the contribution of Drosophila to model human diseases that involve altered metabolism of metals or in which metal dyshomeostasis influence their pathobiology. As a prerequisite to use Drosophila as a model, we will recapitulate and describe the main features of core genes involved in copper and zinc metabolism that are conserved between mammals and flies. Drosophila presents some unique strengths to be at the forefront of neurobiological studies. The number of genetic tools, the possibility to easily test genetic interactions in vivo and the feasibility to perform unbiased genetic and pharmacological screens are some of the most prominent advantages of the fruitfly. In this work, we will pay special attention to the most important results reported in fly models to unveil the role of copper and zinc in cellular degeneration and their influence in the development and progression of human neurodegenerative pathologies such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Friedreich's Ataxia or Menkes, and Wilson's diseases. Finally, we show how these studies performed in the fly have allowed to give further insight into the influence of copper and zinc in the molecular and cellular causes and consequences underlying these diseases as well as the discovery of new therapeutic strategies, which had not yet been described in other model systems.

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“…Genetic and molecular studies in Drosophila can provide valuable insight into the pathogenesis of human diseases, due to the high conservation of key molecular mechanisms underlying biological processes in metazoans, and to the fact that about 77% human disease genes have orthologues in Drosophila [ 1 ]. Thus, targeted expression of mutant human disease genes in Drosophila can recapitulate relevant aspects of the pathology [ 2 , 3 ]. Such expression is frequently achieved by employing the binary Gal4/UAS system, which allows the control of the activity of the gene of interest in a spatiotemporal-restricted manner [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular and cytological analysis of widely-used Gal4 driver lines for Drosophila neurobiology

et al. 2020

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Background The Drosophila central nervous system (CNS) is a convenient model system for the study of the molecular mechanisms of conserved neurobiological processes. The manipulation of gene activity in specific cell types and subtypes of the Drosophila CNS is frequently achieved by employing the binary Gal4/UAS system. However, many Gal4 driver lines available from the Bloomington Drosophila Stock Center (BDSC) and commonly used in Drosophila neurobiology are still not well characterized. Among these are three lines with Gal4 driven by the elav promoter (BDSC #8760, #8765, and #458), one line with Gal4 driven by the repo promoter (BDSC #7415), and the 69B-Gal4 line (BDSC #1774). For most of these lines, the exact insertion sites of the transgenes and the detailed expression patterns of Gal4 are not known. This study is aimed at filling these gaps. Results We have mapped the genomic location of the Gal4-bearing P-elements carried by the BDSC lines #8760, #8765, #458, #7415, and #1774. In addition, for each of these lines, we have analyzed the Gal4-driven GFP expression pattern in the third instar larval CNS and eye-antennal imaginal discs. Localizations of the endogenous Elav and Repo proteins were used as markers of neuronal and glial cells, respectively. Conclusions We provide a mini-atlas of the spatial activity of Gal4 drivers that are widely used for the expression of UAS–target genes in the Drosophila CNS. The data will be helpful for planning experiments with these drivers and for the correct interpretation of the results.

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Studying polyglutamine diseases in Drosophila

Cited by 37 publications

References 288 publications

A phospho-switch at Acinus-Serine⁴³⁷ controls autophagic responses to Cadmium exposure and neurodegenerative stress

A phospho-switch at Acinus-Serine⁴³⁷ controls autophagic responses to Cadmium exposure and neurodegenerative stress

Copper and Zinc Homeostasis: Lessons from Drosophila melanogaster

Molecular and cytological analysis of widely-used Gal4 driver lines for Drosophila neurobiology

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Studying polyglutamine diseases in Drosophila

Cited by 37 publications

References 288 publications

A phospho-switch at Acinus-Serine437 controls autophagic responses to Cadmium exposure and neurodegenerative stress

A phospho-switch at Acinus-Serine437 controls autophagic responses to Cadmium exposure and neurodegenerative stress

Copper and Zinc Homeostasis: Lessons from Drosophila melanogaster

Molecular and cytological analysis of widely-used Gal4 driver lines for Drosophila neurobiology

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A phospho-switch at Acinus-Serine⁴³⁷ controls autophagic responses to Cadmium exposure and neurodegenerative stress

A phospho-switch at Acinus-Serine⁴³⁷ controls autophagic responses to Cadmium exposure and neurodegenerative stress