scholarly journals The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster

2016 ◽  
Vol 6 (12) ◽  
pp. 3859-3867 ◽  
Author(s):  
Youheng Wei ◽  
Brad Reveal ◽  
Weili Cai ◽  
Mary A Lilly
Keyword(s):  
Drosophila Melanogaster ◽  
Amino Acid ◽  
Fat Body ◽  
Critical Role ◽  
Nutrient Stress ◽  
Animal Physiology ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
Baseline Levels

Abstract TORC1 regulates metabolism and growth in response to a large array of upstream inputs. The evolutionarily conserved trimeric GATOR1 complex inhibits TORC1 activity in response to amino acid limitation. In humans, the GATOR1 complex has been implicated in a wide array of pathologies including cancer and hereditary forms of epilepsy. However, the precise role of GATOR1 in animal physiology remains largely undefined. Here, we characterize null mutants of the GATOR1 components nprl2, nprl3, and iml1 in Drosophila melanogaster. We demonstrate that all three mutants have inappropriately high baseline levels of TORC1 activity and decreased adult viability. Consistent with increased TORC1 activity, GATOR1 mutants exhibit a cell autonomous increase in cell growth. Notably, escaper nprl2 and nprl3 mutant adults have a profound locomotion defect. In line with a nonautonomous role in the regulation of systemic metabolism, expressing the Nprl3 protein in the fat body, a nutrient storage organ, and hemocytes but not muscles and neurons rescues the motility of nprl3 mutants. Finally, we show that nprl2 and nprl3 mutants fail to activate autophagy in response to amino acid limitation and are extremely sensitive to both amino acid and complete starvation. Thus, in Drosophila, in addition to maintaining baseline levels of TORC1 activity, the GATOR1 complex has retained a critical role in the response to nutrient stress. In summary, the TORC1 inhibitor GATOR1 contributes to multiple aspects of the development and physiology of Drosophila.

scholarly journals Dual roles for the Drosophila PI 4-kinase Four wheel drive in localizing Rab11 during cytokinesis

2009 ◽  
Vol 187 (6) ◽  
pp. 847-858 ◽  
Author(s):  
Gordon Polevoy ◽  
Ho-Chun Wei ◽  
Raymond Wong ◽  
Zsofia Szentpetery ◽  
Yeun Ju Kim ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Critical Role ◽  
Successful Completion ◽  
Dual Roles ◽  
Recycling Endosome ◽  
Golgi Membranes ◽  
Wheel Drive ◽  
Dividing Cells ◽  
Four Wheel Drive

Successful completion of cytokinesis relies on addition of new membrane, and requires the recycling endosome regulator Rab11, which localizes to the midzone. Despite the critical role of Rab11 in this process, little is known about the formation and composition of Rab11-containing organelles. Here, we identify the phosphatidylinositol (PI) 4-kinase III β Four wheel drive (Fwd) as a key regulator of Rab11 during cytokinesis in Drosophila melanogaster spermatocytes. We show Fwd is required for synthesis of PI 4-phosphate (PI4P) on Golgi membranes and for formation of PI4P-containing secretory organelles that localize to the midzone. Fwd binds and colocalizes with Rab11 on Golgi membranes, and is required for localization of Rab11 in dividing cells. A kinase-dead version of Fwd also binds Rab11 and partially restores cytokinesis to fwd mutant flies. Moreover, activated Rab11 partially suppresses loss of fwd. Our data suggest Fwd plays catalytic and noncatalytic roles in regulating Rab11 during cytokinesis.

The P-element-induced silencing effect of KP transposons is dose dependent in Drosophila melanogaster

Genome ◽  
2011 ◽  
Vol 54 (9) ◽  
pp. 752-762 ◽  
Author(s):  
Alireza Sameny ◽  
John Locke
Keyword(s):  
Drosophila Melanogaster ◽  
Critical Role ◽  
Mutagenic Effect ◽  
P Element ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
P Elements ◽  
Single Well ◽  
Dose Dependent

Transposable elements are found in the genomes of all eukaryotes and play a critical role in altering gene expression and genome organization. In Drosophila melanogaster, transposable P elements are responsible for the phenomenon of hybrid dysgenesis. KP elements, a deletion-derivative of the complete P element, can suppress this mutagenic effect. KP elements can also silence the expression of certain other P-element-mediated transgenes in a process called P-element-dependent silencing (PDS), which is thought to involve the recruitment of heterochromatin proteins. To explore the mechanism of this silencing, we have mobilized KP elements to create a series of strains that contain single, well-defined KP insertions that show PDS. To understand the quantitative role of KP elements in PDS, these single inserts were combined in a series of crosses to obtain genotypes with zero, one, or two KP elements, from which we could examine the effect of KP gene dose. The extent of PDS in these genotypes was shown to be dose dependent in a logarithmic rather than linear fashion. A logarithmic dose dependency is consistent with the KP products interacting with heterochromatic proteins in a concentration-dependent manner such that two molecules are needed to induce gene silencing.

scholarly journals MicroRNAs in Cardiac Autophagy: Small Molecules and Big Role

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 104 ◽  
Author(s):  
Teng Sun ◽  
Meng-Yang Li ◽  
Pei-Feng Li ◽  
Ji-Min Cao
Keyword(s):  
Cardiac Fibrosis ◽  
Heart Diseases ◽  
Critical Role ◽  
Transcriptional Gene Silencing ◽  
Close Link ◽  
Post Transcriptional Gene Silencing ◽  
Evolutionarily Conserved ◽  
Cardiac Disorders ◽  
Cellular Components

Autophagy, which is an evolutionarily conserved process according to the lysosomal degradation of cellular components, plays a critical role in maintaining cell homeostasis. Autophagy and mitochondria autophagy (mitophagy) contribute to the preservation of cardiac homeostasis in physiological settings. However, impaired or excessive autophagy is related to a variety of diseases. Recently, a close link between autophagy and cardiac disorders, including myocardial infarction, cardiac hypertrophy, cardiomyopathy, cardiac fibrosis, and heart failure, has been demonstrated. MicroRNAs (miRNAs) are a class of small non-coding RNAs with a length of approximately 21–22 nucleotides (nt), which are distributed widely in viruses, plants, protists, and animals. They function in mediating the post-transcriptional gene silencing. A growing number of studies have demonstrated that miRNAs regulate cardiac autophagy by suppressing the expression of autophagy-related genes in a targeted manner, which are involved in the pathogenesis of heart diseases. This review summarizes the role of microRNAs in cardiac autophagy and related cardiac disorders. Furthermore, we mainly focused on the autophagy regulation pathways, which consisted of miRNAs and their targeted genes.

scholarly journals Drosophila Gut—A Nexus Between Dietary Restriction and Lifespan

2018 ◽  
Vol 19 (12) ◽  
pp. 3810 ◽  
Author(s):  
Ting Lian ◽  
Qi Wu ◽  
Brian Hodge ◽  
Kenneth Wilson ◽  
Guixiang Yu ◽  
...  
Keyword(s):  
Digestive Tract ◽  
Dietary Restriction ◽  
Healthy Aging ◽  
Fat Body ◽  
Critical Role ◽  
Vital Role ◽  
Intestinal Epithelial ◽  
Beneficial Effects ◽  
Accumulation Of Damage

Aging is often defined as the accumulation of damage at the molecular and cellular levels which, over time, results in marked physiological impairments throughout the organism. Dietary restriction (DR) has been recognized as one of the strongest lifespan extending therapies observed in a wide array of organisms. Recent studies aimed at elucidating how DR promotes healthy aging have demonstrated a vital role of the digestive tract in mediating the beneficial effects of DR. Here, we review how dietary restriction influences gut metabolic homeostasis and immune function. Our discussion is focused on studies of the Drosophila digestive tract, where we describe in detail the potential mechanisms in which DR enhances maintenance of the intestinal epithelial barrier, up-regulates lipid metabolic processes, and improves the ability of the gut to deal with damage or stress. We also examine evidence of a tissue-tissue crosstalk between gut and neighboring organs including brain and fat body. Taken together, we argue that the Drosophila gut plays a critical role in DR-mediated lifespan extension.

Purification and properties of glutamate-phenylpyruvate aminotransferase from the ruminal protozoan Entodinium caudatum

2004 ◽  
Vol 55 (9) ◽  
pp. 991
Author(s):  
Md. Ruhul Amin ◽  
Ryoji Onodera ◽  
R. Islam Khan ◽  
R. John Wallace ◽  
C. Jamie Newbold
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Maximum Activity ◽  
Purification And Properties ◽  
Sds Page ◽  
Wide Range ◽  
S 100 ◽  
A Cell

Entodinium species are important in catabolic protein metabolism by the mixed ruminal microbial population. This study was conducted to purify, and investigate properties of one of the enzymes involved in amino acid metabolism by Entodinium caudatum, glutamate-phenylpyruvate aminotransferase (GPA; EC 2.6.1.64). GPA was purified 74-fold from a cell-free extract by ammonium sulfate precipitation and column chromatography with phenyl-superose, DEAE-Toyopearl 650M, Sephacryl S-100 HR, and Sephadex G-100. The molecular mass of GPA was estimated by SDS–PAGE to be 65.0 kDa. The optimum pH was 6.0 and it was found to be reactive over a wide range of pH from 5.0 to 10.5. Maximum activity of GPA occurred at 45°C and the activity declined at temperatures over 55°C. GPA was stable below 60°C. Aminooxyacetate and phenylhydrazine were highly inhibitory, and SDS, EDTA, and some heavy metal ions also inhibited activity. The purification and characterisation of the enzyme will help to isolate the gene and ultimately to understand the role of GPA in both anabolic and catabolic amino acid metabolism by Entodinium caudatum.

Spalt modifies EGFR-mediated induction of chordotonal precursors in the embryonic PNS of Drosophila promoting the development of oenocytes

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 711-722 ◽  
Author(s):  
T.E. Rusten ◽  
R. Cantera ◽  
J. Urban ◽  
G. Technau ◽  
F.C. Kafatos ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fate ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Dual Function ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
And Migration

Genes of the spalt family encode nuclear zinc finger proteins. In Drosophila melanogaster, they are necessary for the establishment of head/trunk identity, correct tracheal migration and patterning of the wing imaginal disc. Spalt proteins display a predominant pattern of expression in the nervous system, not only in Drosophila but also in species of fish, mouse, frog and human, suggesting an evolutionarily conserved role for these proteins in nervous system development. Here we show that Spalt works as a cell fate switch between two EGFR-induced cell types, the oenocytes and the precursors of the pentascolopodial organ in the embryonic peripheral nervous system. We show that removal of spalt increases the number of scolopodia, as a result of extra secondary recruitment of precursor cells at the expense of the oenocytes. In addition, the absence of spalt causes defects in the normal migration of the pentascolopodial organ. The dual function of spalt in the development of this organ, recruitment of precursors and migration, is reminiscent of its role in tracheal formation and of the role of a spalt homologue, sem-4, in the Caenorhabditis elegans nervous system.

Protein kinase C and chemical-induced abnormal palate development

2005 ◽  
Vol 24 (4) ◽  
pp. 203-214 ◽  
Author(s):  
Chada S Reddy
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Single Gene ◽  
Critical Role ◽  
Early Death ◽  
Palate Development ◽  
Kinase C ◽  
A Cell ◽  
Context Specific

The protein kinase C (PKC) family of proteins mediates the action of growth factors and other ligands by activating a network of transcription factors that bind to TRE sequences in the promoters of many genes that regulate cell proliferation, differentiation, extracellular matrix synthesis, apoptosis and others in a cell type-, isozymeand context-specific manner. The critical role of PKC in embryonic development is indicated by early death of embryos in which one or more of these isozymes are inactivated. Our studies together with others show that palatal PKC signalling is functional and may be essential for normal palate development. Although single gene knockouts have failed to exhibit the cleft palate (CP) phenotype, owing to compensation by other kinases, many chemicals including the mycotoxin, secalonic acid D, disrupt palatal PKC signalling leading to altered palatal mesenchymal gene expression. The potential relevance of such effects to chemical-induced CP is discussed.

scholarly journals Critical role of ASCT2-mediated amino acid metabolism in promoting leukaemia development and progression

2019 ◽  
Vol 1 (3) ◽  
pp. 390-403 ◽  
Author(s):  
Fang Ni ◽  
Wen-Mei Yu ◽  
Zhiguo Li ◽  
Douglas K. Graham ◽  
Lingtao Jin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Critical Role

scholarly journals Caenorhabditis elegans DYF-2, an Orthologue of Human WDR19, Is a Component of the Intraflagellar Transport Machinery in Sensory Cilia

2006 ◽  
Vol 17 (11) ◽  
pp. 4801-4811 ◽  
Author(s):  
Evgeni Efimenko ◽  
Oliver E. Blacque ◽  
Guangshuo Ou ◽  
Courtney J. Haycraft ◽  
Bradley K. Yoder ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Aspartic Acid ◽  
Critical Role ◽  
Intraflagellar Transport ◽  
Bardet Biedl Syndrome ◽  
Evolutionarily Conserved ◽  
Sensory Cilia ◽  
Mutant Phenotypes ◽  
And Function

The intraflagellar transport (IFT) machinery required to build functional cilia consists of a multisubunit complex whose molecular composition, organization, and function are poorly understood. Here, we describe a novel tryptophan-aspartic acid (WD) repeat (WDR) containing IFT protein from Caenorhabditis elegans, DYF-2, that plays a critical role in maintaining the structural and functional integrity of the IFT machinery. We determined the identity of the dyf-2 gene by transgenic rescue of mutant phenotypes and by sequencing of mutant alleles. Loss of DYF-2 function selectively affects the assembly and motility of different IFT components and leads to defects in cilia structure and chemosensation in the nematode. Based on these observations, and the analysis of DYF-2 movement in a Bardet–Biedl syndrome mutant with partially disrupted IFT particles, we conclude that DYF-2 can associate with IFT particle complex B. At the same time, mutations in dyf-2 can interfere with the function of complex A components, suggesting an important role of this protein in the assembly of the IFT particle as a whole. Importantly, the mouse orthologue of DYF-2, WDR19, also localizes to cilia, pointing to an important evolutionarily conserved role for this WDR protein in cilia development and function.

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