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https://www.readbyqxmd.com/read/29051265/regulation-of-notch-signaling-by-rab7-and-rab8-requires-carboxyl-methylation-by-icmt
#1
Helen Court, Ian M Ahearn, Marc Amoyel, Erika A Bach, Mark R Philips
Isoprenylcysteine carboxyl methyltransferase (ICMT) methylesterifies C-terminal prenylcysteine residues of CaaX proteins and some RAB GTPases. Deficiency of either ICMT or NOTCH1 accelerates pancreatic neoplasia in Pdx1-Cre;LSL-Kras(G12D) mice, suggesting that ICMT is required for NOTCH signaling. We used Drosophila melanogaster wing vein and scutellar bristle development to screen Rab proteins predicted to be substrates for ICMT (ste14 in flies). We identified Rab7 and Rab8 as ICMT substrates that when silenced phenocopy ste14 deficiency...
October 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29051039/convolvulus-pluricaulis-shankhapushpi-ameliorates-human-microtubule-associated-protein-tau-hmap%C3%AF-induced-neurotoxicity-in-alzheimer-s-disease-drosophila-model
#2
Kizhakke P Anupama, Olakkaran Shilpa, Anet Antony, Tilagul K Siddanna, Hunasanahally P Gurushankara
Convolvulus pluricaulis (Shankhapushpi) has long been used as traditional herbal medicine in India as nerve tonic. We studied the neuroprotective effects of C. pluricaulis extract (aqueous) against human microtubule-associated protein tau (hMAPτ) induced neurotoxicity in Alzheimer's disease (AD) Drosophila model. We analysed the lifespan, locomotor activity, τ protein level, reactive oxygen species (ROS), lipid peroxidation (LPO), catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities in 10th, 20th and 30th days old control (wild type), τ control tauopathy Drosophila reared on C...
October 16, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29047261/deciphering-the-genes-for-taste-receptors-for-fructose-in-drosophila
#3
Shun Uchizono, Taichi Q Itoh, Haein Kim, Naoki Hamada, Jae Young Kwon, Teiichi Tanimura
Taste sensitivity to sugars plays an essential role in the initiation of feeding behavior. In Drosophila melanogaster, recent studies have identified several gustatory receptor (Gr) genes required for sensing sweet compounds. However, it is as yet undetermined how these GRs function as taste receptors tuned to a wide range of sugars. Among sugars, fructose has been suggested to be detected by a distinct receptor from other sugars. While GR43A has been reported to sense fructose in the brain, it is not expressed in labellar gustatory receptor neurons that show taste response to fructose...
October 17, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/29045822/individual-effects-of-the-copia-and-gypsy-enhancer-and-insulator-on-chromatin-marks-erna-synthesis-and-binding-of-insulator-proteins-in-transfected-genetic-constructs
#4
Daria M Fedoseeva, Olga V Kretova, Maria A Gorbacheva, Nickolai A Tchurikov
Enhancers and insulators are involved in the regulation of gene expression, but the basic underlying mechanisms of action of these elements are unknown. We analyzed the individual effects of the enhancer and the insulator from Drosophila mobile elements copia [enh(copia)] and gypsy using transfected genetic constructs in S2 cells. This system excludes the influence of genomic cis regulatory elements. The enhancer-induced synthesis of 350-1050-nt-long enhancer RNAs (eRNAs) and H3K4me3 and H3K18ac marks, mainly in the region located about 300bp downstream of the enhancer...
October 15, 2017: Gene
https://www.readbyqxmd.com/read/29045748/conserved-asymmetry-underpins-homodimerization-of-dicer-associated-double-stranded-rna-binding-proteins
#5
Alex Heyam, Claire E Coupland, Clément Dégut, Ruth A Haley, Nicola J Baxter, Leonhard Jakob, Pedro M Aguiar, Gunter Meister, Michael P Williamson, Dimitris Lagos, Michael J Plevin
Double-stranded RNA-binding domains (dsRBDs) are commonly found in modular proteins that interact with RNA. Two varieties of dsRBD exist: canonical Type A dsRBDs interact with dsRNA, while non-canonical Type B dsRBDs lack RNA-binding residues and instead interact with other proteins. In higher eukaryotes, the microRNA biogenesis enzyme Dicer forms a 1:1 association with a dsRNA-binding protein (dsRBP). Human Dicer associates with HIV TAR RNA-binding protein (TRBP) or protein activator of PKR (PACT), while Drosophila Dicer-1 associates with Loquacious (Loqs)...
October 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040648/molecular-basis-for-asymmetry-sensing-of-sirnas-by-the-drosophila-loqs-pd-dcr-2-complex-in-rna-interference
#6
Jan-Niklas Tants, Stephanie Fesser, Thomas Kern, Ralf Stehle, Arie Geerlof, Christoph Wunderlich, Michael Juen, Christoph Hartlmüller, Romy Böttcher, Stefan Kunzelmann, Oliver Lange, Christoph Kreutz, Klaus Förstemann, Michael Sattler
RNA interference defends against RNA viruses and retro-elements within an organism's genome. It is triggered by duplex siRNAs, of which one strand is selected to confer sequence-specificity to the RNA induced silencing complex (RISC). In Drosophila, Dicer-2 (Dcr-2) and the double-stranded RNA binding domain (dsRBD) protein R2D2 form the RISC loading complex (RLC) and select one strand of exogenous siRNAs according to the relative thermodynamic stability of base-pairing at either end. Through genome editing we demonstrate that Loqs-PD, the Drosophila homolog of human TAR RNA binding protein (TRBP) and a paralog of R2D2, forms an alternative RLC with Dcr-2 that is required for strand choice of endogenous siRNAs in S2 cells...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29038305/variations-in-basement-membrane-mechanics-are-linked-to-epithelial-morphogenesis
#7
Julien Chlasta, Pascale Milani, Gaël Runel, Jean-Luc Duteyrat, Leticia Arias, Laurie-Anne Lamiré, Arezki Boudaoud, Muriel Grammont
The regulation of morphogenesis by the basement membrane (BM) may rely on changes in its mechanical properties. To test this, we developed an AFM-based method to measure BM mechanical stiffness during two key processes in Drosophila ovarian follicle development. First, follicle elongation depends on epithelial cells that collectively migrate secreting BM fibrils perpendicularly to the anteroposterior axis. Our data show that BM stiffness increases during this migration and that fibril incorporation enhances BM stiffness...
October 16, 2017: Development
https://www.readbyqxmd.com/read/29036346/opbp-is-a-new-architectural-insulator-protein-required-for-ribosomal-gene-expression
#8
Nikolay Zolotarev, Oksana Maksimenko, Olga Kyrchanova, Elena Sokolinskaya, Igor Osadchiy, Charles Girardot, Artem Bonchuk, Lucia Ciglar, Eileen E M Furlong, Pavel Georgiev
A special class of poorly characterized architectural proteins is required for chromatin topology and enhancer-promoter interactions. Here, we identify Opbp as a new Drosophila architectural protein, interacting with CP190 both in vivo and in vitro. Opbp binds to a very restrictive set of genomic regions, through a rare sequence specific motif. These sites are co-bound by CP190 in vivo, and generally located at bidirectional promoters of ribosomal protein genes. We show that Opbp is essential for viability, and loss of opbp function, or destruction of its motif, leads to reduced ribosomal protein gene expression, indicating a functional role in promoter activation...
September 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29036187/analysis-of-transient-hypermorphic-activity-of-e-spl-d-during-r8-specification
#9
Adam T Majot, Ashok P Bidwai
Drosophila atonal (ato) is required for the specification of founding R8 photoreceptors during retinal development. ato is regulated via dual eye-specific enhancers; ato-3' is subject to initial induction whereas 5'-ato facilitates Notch-mediated autoregulation. Notch is further utilized to induce bHLH repressors of the E(spl) locus to restrict Ato from its initial broad expression to individual cells. Although Notch operates in two, distinct phases, it has remained unclear how the two phases maintain independence from one another...
2017: PloS One
https://www.readbyqxmd.com/read/29035200/small-conductance-ca-2-activated-k-channels-induce-the-firing-pause-periods-during-the-activation-of-drosophila-nociceptive-neurons
#10
Koun Onodera, Shumpei Baba, Akira Murakami, Tadashi Uemura, Tadao Usui
In Drosophila larvae, Class IV sensory neurons respond to noxious thermal stimuli and provoke heat avoidance behavior. Previously, we showed that the activated neurons displayed characteristic fluctuations of firing rates which consisted of repetitive high-frequency spike trains and subsequent pause periods, and we proposed that the firing rate fluctuations enhanced the heat avoidance (Terada et al., 2016). Here, we further substantiate this idea by showing that the pause periods and the frequency of fluctuations are regulated by small conductance Ca(2+)-activated K(+) (SK) channels, and the SK knockdown larvae display faster heat avoidance than control larvae...
October 16, 2017: ELife
https://www.readbyqxmd.com/read/29030610/angiotensin-converting-enzyme-ance-is-cooperatively-regulated-by-mad-and-pannier-in-drosophila-imaginal-discs
#11
Ah-Ram Kim, Eun-Bee Choi, Mi-Young Kim, Kwang-Wook Choi
Angiotensin-converting enzyme (ACE) is an evolutionarily conserved peptidyl dipeptidase. Mammalian ACE converts angiotensin I to the active vasoconstrictor angiotensin II, thus playing a critical role for homeostasis of the renin-angiotensin system. In Drosophila, the ACE homolog Ance is expressed in specific regions of developing organs, but its regulatory mechanism has not been identified. Here we provide evidence that Ance expression is regulated by a combination of Mad and Pannier (Pnr) in imaginal discs...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29030483/rbpj-cbf1-interacts-with-l3mbtl3-mbt1-to-promote-repression-of-notch-signaling-via-histone-demethylase-kdm1a-lsd1
#12
Tao Xu, Sung-Soo Park, Benedetto Daniele Giaimo, Daniel Hall, Francesca Ferrante, Diana M Ho, Kazuya Hori, Lucas Anhezini, Iris Ertl, Marek Bartkuhn, Honglai Zhang, Eléna Milon, Kimberly Ha, Kevin P Conlon, Rork Kuick, Brandon Govindarajoo, Yang Zhang, Yuqing Sun, Yali Dou, Venkatesha Basrur, Kojo Sj Elenitoba-Johnson, Alexey I Nesvizhskii, Julian Ceron, Cheng-Yu Lee, Tilman Borggrefe, Rhett A Kovall, Jean-François Rual
Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. Upon ligand binding, the Notch intracellular domain (NOTCH ICD) translocates into the nucleus and forms a complex with the transcription factor RBPJ (also known as CBF1 or CSL) to activate expression of Notch target genes. In the absence of a Notch signal, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 (also known as MBT1) as a novel RBPJ interactor...
October 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29029226/new-insights-into-the-genetic-basis-of-monge-s-disease-and-adaptation-to-high-altitude
#13
Tsering Stobdan, Ali Akbari, Priti Azad, Dan Zhou, Orit Poulsen, Otto Appenzeller, Gustavo F Gonzales, Amalio Telenti, Emily H M Wong, Shubham Saini, Ewen F Kirkness, J Craig Venter, Vineet Bafna, Gabriel G Haddad
Human high-altitude (HA) adaptation or mal-adaptation is explored to understand the physiology, pathophysiology and molecular mechanisms that underlie long-term exposure to hypoxia. Here we report the results of an analysis of the largest whole-genome-sequencing of Chronic Mountain Sickness (CMS) and non-CMS individuals, identified candidate genes and functionally validated these candidates in a genetic model system (Drosophila). We used PreCIOSS algorithm that uses Haplotype Allele Frequency score to separate haplotypes carrying the favored allele from the non-carriers and accordingly prioritize genes associated with the CMS or non-CMS phenotype...
September 19, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29025914/dendritic-cytoskeletal-architecture-is-modulated-by-combinatorial-transcriptional-regulation-in-drosophila-melanogaster
#14
Ravi Das, Shatabdi Bhattacharjee, Atit A Patel, Jenna M Harris, Surajit Bhattacharya, Jamin M Letcher, Sarah G Clark, Sumit Nanda, Eswar Prasad R Iyer, Giorgio A Ascoli, Daniel N Cox
Transcription factors (TFs) have emerged as essential cell autonomous mediators of sub-type specific dendritogenesis, however, the downstream effectors of these TFs remain largely unknown, as are the cellular events that TFs control to direct morphological change. As dendritic morphology is largely dictated by the organization of the actin and microtubule (MT) cytoskeletons, elucidating TF-mediated cytoskeletal regulatory programs is key to understanding molecular control of diverse dendritic morphologies. Previous studies in Drosophila melanogaster have demonstrated that the conserved TFs Cut and Knot exert combinatorial control over aspects of dendritic cytoskeleton development, promoting actin- and MT-based arbor morphology, respectively...
October 12, 2017: Genetics
https://www.readbyqxmd.com/read/29023471/combinatorial-action-of-grainyhead-extradenticle-and-notch-in-regulating-hox-mediated-apoptosis-in-drosophila-larval-cns
#15
Risha Khandelwal, Rashmi Sipani, Sriivatsan Govinda Rajan, Raviranjan Kumar, Rohit Joshi
Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis is not understood. Our studies with Abdominal-A (Abd-A) mediated larval neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd), a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling transcriptionally contribute to expression of RHG family of apoptotic genes. We find that Grh, AbdA, and Exd function together at multiple motifs on the apoptotic enhancer...
October 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29021745/tyramine-actions-on-drosophila-flight-behavior-are-affected-by-a-glial-dehydrogenase-reductase
#16
Stefanie Ryglewski, Carsten Duch, Benjamin Altenhein
The biogenic amines octopamine (OA) and tyramine (TA) modulate insect motor behavior in an antagonistic manner. OA generally enhances locomotor behaviors such as Drosophila larval crawling and flight, whereas TA decreases locomotor activity. However, the mechanisms and cellular targets of TA modulation of locomotor activity are incompletely understood. This study combines immunocytochemistry, genetics and flight behavioral assays in the Drosophila model system to test the role of a candidate enzyme for TA catabolism, named Nazgul (Naz), in flight motor behavioral control...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/29021216/multiple-interactions-are-involved-in-a-highly-specific-association-of-the-mod-mdg4-67-2-isoform-with-the-su-hw-sites-in-drosophila
#17
Larisa Melnikova, Margarita Kostyuchenko, Varvara Molodina, Alexander Parshikov, Pavel Georgiev, Anton Golovnin
The best-studied Drosophila insulator complex consists of two BTB-containing proteins, the Mod(mdg4)-67.2 isoform and CP190, which are recruited to the chromatin through interactions with the DNA-binding Su(Hw) protein. It was shown previously that Mod(mdg4)-67.2 is critical for the enhancer-blocking activity of the Su(Hw) insulators and it differs from more than 30 other Mod(mdg4) isoforms by the C-terminal domain required for a specific interaction with Su(Hw) only. The mechanism of the highly specific association between Mod(mdg4)-67...
October 2017: Open Biology
https://www.readbyqxmd.com/read/29016849/differential-protective-effects-of-connective-tissue-growth-factor-against-a%C3%AE-neurotoxicity-on-neurons-and-glia
#18
Cheng-Ning Yang, Min-Fang Wu, Chung-Chih Liu, Wei-Hung Jung, Yu-Chin Chang, Wang-Pao Lee, Young-Ji Shiao, Chia-Lin Wu, Horng-Huei Liou, Sze-Kwan Lin, Chih-Chiang Chan
Impaired clearance of amyloid-β peptide (Aβ) leads to abnormal extracellular accumulation of this neurotoxic protein that drives neurodegeneration in sporadic Alzheimer's disease (AD). Connective tissue growth factor (CTGF/CCN2) expression is elevated in plaque-surrounding astrocytes in AD patients. However, the role of CTGF in AD pathogenesis remains unclear. Here we characterized the neuroprotective activity of CTGF. We found that CTGF facilitated Aβ uptake and subsequent degradation within primary glia and neuroblastoma cells...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28994789/focal-macropatch-recordings-of-synaptic-currents-from-the-drosophila-larval-neuromuscular-junction
#19
Alexander Vasin, Maria Bykhovskaia
Drosophila neuromuscular junction (NMJ) is an excellent model system to study glutamatergic synaptic transmission. We describe the technique of focal macropatch recordings of synaptic currents from visualized boutons at the Drosophila larval NMJ. This technique requires customized fabrication of recording micropipettes, as well as a compound microscope equipped with a high magnification, long-distance water immersion objective, differential interference contrast (DIC) optics, and a fluorescent attachment. The recording electrode is positioned on the top of a selected synaptic bouton visualized with DIC optics, epi-fluorescence, or both...
September 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28993910/improved-process-conditions-for-increasing-expression-of-mhc-class-ii-protein-from-a-stable-drosophila-s2-cell-line
#20
Xiao Shen, Danijel Dojcinovic, Lucia Baldi, David L Hacker, Immanuel F Luescher, Florian M Wurm
OBJECTIVES: To investigate the effects of operational process conditions on expression of MHC class II protein from a stable Drosophila S2 cell line. RESULTS: When the Drosophila S2 cells were grown in vented orbitally shaken TubeSpin bioreactor 600 containers, cell growth was improved three-fold and the yield of recombinant major histocompatibility (MHC) class II protein (HLA-DR12xHis) increased four-fold over the levels observed for the same cells cultivated in roller bottles (RB) without vented caps...
October 9, 2017: Biotechnology Letters
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