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https://www.readbyqxmd.com/read/28406902/bicaudal-c-mutation-causes-myc-and-tor-pathway-up-regulation-and-polycystic-kidney-disease-like-phenotypes-in-drosophila
#1
Chiara Gamberi, David R Hipfner, Marie Trudel, William D Lubell
Progressive cystic kidney degeneration underlies diverse renal diseases, including the most common cause of kidney failure, autosomal dominant Polycystic Kidney Disease (PKD). Genetic analyses of patients and animal models have identified several key drivers of this disease. The precise molecular and cellular changes underlying cystogenesis remain, however, elusive. Drosophila mutants lacking the translational regulator Bicaudal C (BicC, the fly ortholog of vertebrate BICC1 implicated in renal cystogenesis) exhibited progressive cystic degeneration of the renal tubules (so called "Malpighian" tubules) and reduced renal function...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28363744/dref-plays-multiple-roles-during-drosophila-development
#2
REVIEW
Nguyen Trong Tue, Yasuhide Yoshioka, Megumi Mizoguchi, Hideki Yoshida, Mario Zurita, Masamitsu Yamaguchi
DREF was originally identified as a transcription factor that coordinately regulates the expression of DNA replication- and proliferation-related genes in Drosophila. Subsequent studies demonstrated that DREF is involved in tumor suppressor pathways including p53 and Hippo signaling. DREF also regulates the expression of genes encoding components of the JNK and EGFR pathways during Drosophila development. DREF itself is under the control of the TOR pathway during cell and tissue growth responding to nutrition...
March 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28317899/minocycline-treatment-suppresses-juvenile-development-and-growth-by-attenuating-insulin-tor-signaling-in-drosophila-animal-model
#3
Hyun Myoung Yun, Sujin Noh, Seogang Hyun
Minocycline is a broad spectrum, semi-synthetic tetracycline analog that is used to treat bacterial infection. Recently, this drug has been receiving increasing attention for its non-antibiotic properties, including anti-inflammatory, tumor suppressive, and neuroprotective effects. Drosophila is a useful model organism for studying human metabolism and disease. In this study, we investigated the effects of minocycline on juvenile development and growth in Drosophila. Feeding minocycline to Drosophila larvae suppresses larval body growth and delays the timing of pupation in a dose-dependent manner...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28241077/%C3%AE-amanitin-resistance-in-drosophila-melanogaster-a-genome-wide-association-approach
#4
Chelsea L Mitchell, Catrina E Latuszek, Kara R Vogel, Ian M Greenlund, Rebecca E Hobmeier, Olivia K Ingram, Shannon R Dufek, Jared L Pecore, Felicia R Nip, Zachary J Johnson, Xiaohui Ji, Hairong Wei, Oliver Gailing, Thomas Werner
We investigated the mechanisms of mushroom toxin resistance in the Drosophila Genetic Reference Panel (DGRP) fly lines, using genome-wide association studies (GWAS). While Drosophila melanogaster avoids mushrooms in nature, some lines are surprisingly resistant to α-amanitin-a toxin found solely in mushrooms. This resistance may represent a pre-adaptation, which might enable this species to invade the mushroom niche in the future. Although our previous microarray study had strongly suggested that pesticide-metabolizing detoxification genes confer α-amanitin resistance in a Taiwanese D...
2017: PloS One
https://www.readbyqxmd.com/read/28196106/tor-signaling-pathway-and-autophagy-are-involved-in-the-regulation-of-circadian-rhythms-in-behavior-and-plasticity-of-l2-interneurons-in-the-brain-of-drosophila-melanogaster
#5
Ewelina Kijak, Elżbieta Pyza
Drosophila melanogaster is a common model used to study circadian rhythms in behavior and circadian clocks. However, numerous circadian rhythms have also been detected in non-clock neurons, especially in the first optic neuropil (lamina) of the fly's visual system. Such rhythms have been observed in the number of synapses and in the structure of interneurons, which exhibit changes in size and shape in a circadian manner. Although the patterns of these changes are known, the mechanism remains unclear. In the present study, we investigated the role of the TOR signaling pathway and autophagy in regulating circadian rhythms based on the behavior and structural plasticity of the lamina L2 monopolar cell dendritic trees...
2017: PloS One
https://www.readbyqxmd.com/read/28121986/nutrient-dependent-endocycling-in-steroidogenic-tissue-dictates-timing-of-metamorphosis-in-drosophila-melanogaster
#6
Yuya Ohhara, Satoru Kobayashi, Naoki Yamanaka
Many animals have an intrinsic growth checkpoint during juvenile development, after which an irreversible decision is made to upregulate steroidogenesis, triggering the metamorphic juvenile-to-adult transition. However, a molecular process underlying such a critical developmental decision remains obscure. Here we show that nutrient-dependent endocycling in steroidogenic cells provides the machinery necessary for irreversible activation of metamorphosis in Drosophila melanogaster. Endocycle progression in cells of the prothoracic gland (PG) is tightly coupled with the growth checkpoint, and block of endocycle in PG cells causes larval developmental arrest due to reduction in biosynthesis of the steroid hormone ecdysone...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28077876/microenvironmental-autophagy-promotes-tumour-growth
#7
Nadja S Katheder, Rojyar Khezri, Fergal O'Farrell, Sebastian W Schultz, Ashish Jain, Mohammed M Rahman, Kay O Schink, Theodossis A Theodossiou, Terje Johansen, Gábor Juhász, David Bilder, Andreas Brech, Harald Stenmark, Tor Erik Rusten
As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues. Tumour growth can be pharmacologically restrained using autophagy inhibitors, and early-stage tumour growth and invasion are genetically dependent on autophagy within the local tumour microenvironment...
January 19, 2017: Nature
https://www.readbyqxmd.com/read/27916456/acute-fasting-regulates-retrograde-synaptic-enhancement-through-a-4e-bp-dependent-mechanism
#8
Grant Kauwe, Kazuya Tsurudome, Jay Penney, Megumi Mori, Lindsay Gray, Mario R Calderon, Fatima Elazouzzi, Nicole Chicoine, Nahum Sonenberg, A Pejmun Haghighi
While beneficial effects of fasting on organismal function and health are well appreciated, we know little about the molecular details of how fasting influences synaptic function and plasticity. Our genetic and electrophysiological experiments demonstrate that acute fasting blocks retrograde synaptic enhancement that is normally triggered as a result of reduction in postsynaptic receptor function at the Drosophila larval neuromuscular junction (NMJ). This negative regulation critically depends on transcriptional enhancement of eukaryotic initiation factor 4E binding protein (4E-BP) under the control of the transcription factor Forkhead box O (Foxo)...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/27909242/beneficial-effects-of-rapamycin-in-a-drosophila-model-for-hereditary-spastic-paraplegia
#9
Shiyu Xu, Michael Stern, James A McNew
The locomotor deficits in the group of diseases referred to as hereditary spastic paraplegia (HSP) reflect degeneration of upper motor neurons, but the mechanisms underlying this neurodegeneration are unknown. We established a Drosophila model for HSP, atlastin (atl), which encodes an ER fusion protein. Here, we show that neuronal atl loss causes degeneration of specific thoracic muscles that is preceded by other pathologies, including accumulation of aggregates containing polyubiquitin, increased generation of reactive oxygen species and activation of the JNK-Foxo stress response pathway...
January 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/27904993/molecular-mechanisms-of-heart-failure-insights-from-drosophila
#10
Shasha Zhu, Zhe Han, Yan Luo, Yulin Chen, Qun Zeng, Xiushan Wu, Wuzhou Yuan
Heart failure places an enormous burden on health and economic systems worldwide. It is a complex disease that is profoundly influenced by both genetic and environmental factors. Neither the molecular mechanisms underlying heart failure nor effective prevention strategies are fully understood. Fortunately, relevant aspects of human heart failure can be experimentally studied in tractable model animals, including the fruit fly, Drosophila, allowing the in vivo application of powerful and sophisticated molecular genetic and physiological approaches...
January 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/27741510/rapamycin-enhances-survival-in-a-drosophila-model-of-mitochondrial-disease
#11
Adrienne Wang, Jacob Mouser, Jason Pitt, Daniel Promislow, Matt Kaeberlein
Pediatric mitochondrial disorders are a devastating category of diseases caused by deficiencies in mitochondrial function. Leigh Syndrome (LS) is the most common of these diseases with symptoms typically appearing within the first year of birth and progressing rapidly until death, usually by 6-7 years of age. Our lab has recently shown that genetic inhibition of the mechanistic target of rapamycin (TOR) rescues the short lifespan of yeast mutants with defective mitochondrial function, and that pharmacological inhibition of TOR by administration of rapamycin significantly rescues the shortened lifespan, neurological symptoms, and neurodegeneration in a mouse model of LS...
December 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27713427/insulin-and-tor-signal-in-parallel-through-foxo-and-s6k-to-promote-epithelial-wound-healing
#12
Parisa Kakanj, Bernard Moussian, Sebastian Grönke, Victor Bustos, Sabine A Eming, Linda Partridge, Maria Leptin
The TOR and Insulin/IGF signalling (IIS) network controls growth, metabolism and ageing. Although reducing TOR or insulin signalling can be beneficial for ageing, it can be detrimental for wound healing, but the reasons for this difference are unknown. Here we show that IIS is activated in the cells surrounding an epidermal wound in Drosophila melanogaster larvae, resulting in PI3K activation and redistribution of the transcription factor FOXO. Insulin and TOR signalling are independently necessary for normal wound healing, with FOXO and S6K as their respective effectors...
October 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27693629/activation-of-the-tor-myc-signaling-axis-in-intestinal-stem-and-progenitor-cells-affects-longevity-stress-resistance-and-metabolism-in-drosophila
#13
Olha M Strilbytska, Uliana V Semaniuk, Kenneth B Storey, Bruce A Edgar, Oleh V Lushchak
The TOR (target of rapamycin) signaling pathway and the transcriptional factor Myc play important roles in growth control. Myc acts, in part, as a downstream target of TOR to regulate the activity and functioning of stem cells. Here we explore the role of TOR-Myc axis in stem and progenitor cells in the regulation of lifespan, stress resistance and metabolism in Drosophila. We found that both overexpression of rheb and myc-rheb in midgut stem and progenitor cells decreased the lifespan and starvation resistance of flies...
January 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/27633989/somatic-stem-cell-differentiation-is-regulated-by-pi3k-tor-signaling-in-response-to-local-cues
#14
Marc Amoyel, Kenzo-Hugo Hillion, Shally R Margolis, Erika A Bach
Stem cells reside in niches that provide signals to maintain self-renewal, and differentiation is viewed as a passive process that depends on loss of access to these signals. Here, we demonstrate that the differentiation of somatic cyst stem cells (CySCs) in the Drosophila testis is actively promoted by PI3K/Tor signaling, as CySCs lacking PI3K/Tor activity cannot differentiate properly. We find that an insulin peptide produced by somatic cells immediately outside of the stem cell niche acts locally to promote somatic differentiation through Insulin-like receptor (InR) activation...
November 1, 2016: Development
https://www.readbyqxmd.com/read/27590505/autophagy-regulates-the-survival-of-cells-with-chromosomal-instability
#15
Dawei Liu, Zeeshan Shaukat, Tianqi Xu, Donna Denton, Robert Saint, Stephen Gregory
Chromosomal instability (CIN) refers to genomic instability in which cells have gained or lost chromosomes or chromosomal fragments. A high level of CIN is common in solid tumours and is associated with cancer drug resistance and poor prognosis. The impact of CIN-induced stress and the resulting cellular responses are only just beginning to emerge. Using proliferating tissue in Drosophila as a model, we found that autophagy is activated in CIN cells and is necessary for their survival. Specifically, increasing the removal of defective mitochondria by mitophagy is able to lower levels of reactive oxygen species and the resultant cellular damage that is normally seen in CIN cells...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27551717/a-molecular-probe-for-the-detection-of-polar-lipids-in-live-cells
#16
Christie A Bader, Tetyana Shandala, Elizabeth A Carter, Angela Ivask, Taryn Guinan, Shane M Hickey, Melissa V Werrett, Phillip J Wright, Peter V Simpson, Stefano Stagni, Nicolas H Voelcker, Peter A Lay, Massimiliano Massi, Sally E Plush, Douglas A Brooks
Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells...
2016: PloS One
https://www.readbyqxmd.com/read/27487474/selective-endosomal-microautophagy-is-starvation-inducible-in-drosophila
#17
Anindita Mukherjee, Bindi Patel, Hiroshi Koga, Ana Maria Cuervo, Andreas Jenny
Autophagy delivers cytosolic components to lysosomes for degradation and is thus essential for cellular homeostasis and to cope with different stressors. As such, autophagy counteracts various human diseases and its reduction leads to aging-like phenotypes. Macroautophagy (MA) can selectively degrade organelles or aggregated proteins, whereas selective degradation of single proteins has only been described for chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI). These 2 autophagic pathways are specific for proteins containing KFERQ-related targeting motifs...
November 2016: Autophagy
https://www.readbyqxmd.com/read/27467079/genetic-screen-in-drosophila-larvae-links-ird1-function-to-toll-signaling-in-the-fat-body-and-hemocyte-motility
#18
Martin R Schmid, Ines Anderl, Hoa T M Vo, Susanna Valanne, Hairu Yang, Jesper Kronhamn, Mika Rämet, Tor Erik Rusten, Dan Hultmark
To understand how Toll signaling controls the activation of a cellular immune response in Drosophila blood cells (hemocytes), we carried out a genetic modifier screen, looking for deletions that suppress or enhance the mobilization of sessile hemocytes by the gain-of-function mutation Toll10b (Tl10b). Here we describe the results from chromosome arm 3R, where five regions strongly suppressed this phenotype. We identified the specific genes immune response deficient 1 (ird1), headcase (hdc) and possibly Rab23 as suppressors, and we studied the role of ird1 in more detail...
2016: PloS One
https://www.readbyqxmd.com/read/27395408/fus-linked-essential-tremor-associated-with-motor-dysfunction-in-drosophila
#19
Murni Tio, Rujing Wen, Yih Lin Lim, Huashan Wang, Shuo-Chien Ling, Yi Zhao, Eng-King Tan
Essential tremor (ET) is one of the most common adult-onset neurological disorders which produce motor and non-motor symptoms. To date, there are no gold standard pathological hallmarks of ET, and despite a strong genetic contribution toward ET development, only a few pathogenic mutations have been identified. Recently, a pathogenic FUS-Q290X mutation has been reported in a large ET-affected family; however, the pathophysiologic mechanism underlying FUS-linked ET is unknown. Here, we generated transgenic Drosophila expressing hFUS-WT and hFUS-Q290X and targeted their expression in different tissues...
November 2016: Human Genetics
https://www.readbyqxmd.com/read/27326933/a-drosophila-genome-wide-screen-identifies-regulators-of-steroid-hormone-production-and-developmental-timing
#20
E Thomas Danielsen, Morten E Moeller, Naoki Yamanaka, Qiuxiang Ou, Janne M Laursen, Caecilie Soenderholm, Ran Zhuo, Brian Phelps, Kevin Tang, Jie Zeng, Shu Kondo, Christian H Nielsen, Eva B Harvald, Nils J Faergeman, Macy J Haley, Kyle A O'Connor, Kirst King-Jones, Michael B O'Connor, Kim F Rewitz
Steroid hormones control important developmental processes and are linked to many diseases. To systematically identify genes and pathways required for steroid production, we performed a Drosophila genome-wide in vivo RNAi screen and identified 1,906 genes with potential roles in steroidogenesis and developmental timing. Here, we use our screen as a resource to identify mechanisms regulating intracellular levels of cholesterol, a substrate for steroidogenesis. We identify a conserved fatty acid elongase that underlies a mechanism that adjusts cholesterol trafficking and steroidogenesis with nutrition and developmental programs...
June 20, 2016: Developmental Cell
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