0000000000076770
AUTHOR
Stephan Schneuwly
Altered lipid metabolism in a Drosophila model of Friedreich's ataxia
13 páginas, 5 figuras.-- et al.
The DrosDel Collection
Abstract We describe a collection of P-element insertions that have considerable utility for generating custom chromosomal aberrations in Drosophila melanogaster. We have mobilized a pair of engineered P elements, p{RS3} and p{RS5}, to collect 3243 lines unambiguously mapped to the Drosophila genome sequence. The collection contains, on average, an element every 35 kb. We demonstrate the utility of the collection for generating custom chromosomal deletions that have their end points mapped, with base-pair resolution, to the genome sequence. The collection was generated in an isogenic strain, thus affording a uniform background for screens where sensitivity to genetic background is high. The…
Disarrangement of Endoplasmic reticulum-mitochondria communication impairs Ca2+ homeostasis in FRDA
AbstractFriedreich ataxia (FRDA) is a neurodegenerative disorder characterized by neuromuscular and neurological manifestations. It is caused by mutations in gene FXN, which results in loss of the mitochondrial protein frataxin. Endoplasmic Reticulum-mitochondria associated membranes (MAMs) are inter-organelle structures involved in the regulation of essential cellular processes, including lipid metabolism and calcium signaling. In the present study, we have analyzed in both, unicellular and multicellular models of FRDA, an analysis of calcium management and of integrity of MAMs. We observed that function of MAMs is compromised in our cellular model of FRDA, which was improved upon treatmen…
Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels
10 pages, 5 figures. 21779322[PubMed] PMCID: PMC3136927
Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model
Friedreich ataxia (FRDA) is a neurodegenerative disorder characterized by neuromuscular and neurological manifestations. It is caused by mutations in the FXN gene, which results in loss of the mitochondrial protein frataxin. Endoplasmic Reticulum-mitochondria associated membranes (MAMs) are inter-organelle structures involved in the regulation of essential cellular processes, including lipid metabolism and calcium signaling. In the present study, we have analyzed in both, unicellular and multicellular models of FRDA, calcium management and integrity of MAMs. We observed that function of MAMs is compromised in our cellular model of FRDA, which was improved upon treatment with antioxidants. I…
Causative role of oxidative stress in a Drosophila model of Friedreich ataxia
Friedreich ataxia (FA), the most common form of hereditary ataxia, is caused by a deficit in the mitochondrial protein frataxin. While several hypotheses have been suggested, frataxin function is not well understood. Oxidative stress has been suggested to play a role in the pathophysiology of FA, but this view has been recently questioned, and its link to frataxin is unclear. Here, we report the use of RNA interference (RNAi) to suppress the Drosophila frataxin gene (fh) expression. This model system parallels the situation in FA patients, namely a moderate systemic reduction of frataxin levels compatible with normal embryonic development. Under these conditions, fh-RNAi flies showed a shor…
GAL4-responsive UAS- tau as a tool for studying the anatomy and development of the Drosophila central nervous system
To improve the quality of cytoplasmic labelling of GAL4-expressing cells in Drosophila enhancer-trap and transgenic strains, a new GAL4-responsive reporter UAS-tau, which features a bovine tau cDNA under control of a yeast upstream activation sequence (UAS), was tested. Tau, a microtubule-associated protein, is distributed actively and evenly into all cellular processes. Monoclonal anti-bovine Tau antibody reveals the axonal structure of the labelled cells with detail similar to that of Golgi impregnation. We demonstrate that the UAS-tau system is especially useful for studying processes of differentiation and reorganisation of identified neurones during postembryonic development.