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amino acid starvation

Joseph Amick, Arun Kumar Tharkeshwar, Catherine Amaya, Shawn M Ferguson
C9orf72 mutations are a major cause of amyotrophic lateral sclerosis and frontotemporal dementia. The C9orf72 protein undergoes regulated recruitment to lysosomes and has been broadly implicated in control of lysosome homeostasis. However, although evidence strongly supports an important function for C9orf72 at lysosomes, little is known about the lysosome recruitment mechanism. In this study, we identify an essential role for WDR41, a prominent C9orf72 interacting protein, in the C9orf72 lysosome recruitment mechanism...
July 11, 2018: Molecular Biology of the Cell
Hao Ding, Mélissa Caza, Yifei Dong, Arif A Arif, Linda C Horianopoulos, Guanggan Hu, Pauline Johnson, James W Kronstad
The process of autophagy is conserved among all eukaryotes from yeast to humans, and is mainly responsible for bulk degradation of cellular contents and nutrient recycling during starvation. Autophagy has been suggested to play a role in the pathogenesis of the opportunistic human fungal pathogen Cryptococcus neoformans, potentially through a contribution to the export of virulence factors. In this study, we show that deletion of each of the ATG1 , ATG7 , ATG8 , and ATG9 genes in C. neoformans leads to autophagy-related phenotypes including impaired amino acid homeostasis under nitrogen starvation...
July 9, 2018: Infection and Immunity
Angelina Huseinovic, Stefan J Dekker, Bob Boogaard, Nico P E Vermeulen, Jan M Kooter, J Chris Vos
In yeast, toxicity of acetaminophen (APAP), a frequently used analgesic and antipyretic drug, depends on ubiquitin-controlled processes. Previously, we showed a remarkable overlap in toxicity profiles between APAP and tyrosine, and a similarity with drugs like rapamycin and quinine, which induce degradation of the amino acid permease Tat2. Therefore, we investigated in yeast whether APAP reduced the expression levels of amino acid permeases. The protein levels of Tat2, Tat1, Mup1 and Hip1 were reduced, while the expression of the general permease Gap1 was increased, consistent with a nutrient starvation response...
July 5, 2018: Amino Acids
Hoa Q Pham, Kazuaki Yoshioka, Hiromi Mohri, Hiroki Nakata, Sho Aki, Kazuhiro Ishimaru, Noriko Takuwa, Yoh Takuwa
Phosphatidylinositol 3-phosphate (PI(3)P) is the predominant phosphoinositide species in early endosomes and autophagosomes, in which PI(3)P dictates traffic of these organelles. Phosphoinositide levels are tightly regulated by lipid-kinases and -phosphatases; however, a phosphatase that converts PI(3)P back to phosphatidylinositol in the endosomal and autophagosomal compartments is not fully understood. We investigated the subcellular distribution and functions of myotubularin-related protein-4 (MTMR4), which is distinct among other MTMRs in that it possesses a PI(3)P-binding FYVE domain, in lung alveolar epithelium-derived A549 cells...
July 2, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Alec M Judd, Melinda K Matthews, Rachel Hughes, Madeline Veloz, Corinne E Sexton, John M Chaston
Animal-associated microorganisms ('microbiota') dramatically influence nutritional and physiological traits of their hosts. To expand our understanding of such influences, we predicted bacterial genes that influence a quantitative animal trait by a comparative genomic approach and extended these predictions via mutant analysis. We focus on D. melanogaster starvation resistance (SR). We first confirmed that D. melanogaster SR responds to the microbiota by demonstrating that bacteria-free flies have greater SR than flies bearing a standard 5-species microbial community, and extended this analysis by revealing species-specific influence of 38 genome-sequenced bacterial species on D...
June 22, 2018: Applied and Environmental Microbiology
Shaoyun Dong, Joshua Zhang, Diane M Beckles
Plant carbon status is optimized for normal growth but is affected by abiotic stress. Here, we used 14 C-labeling to provide the first holistic picture of carbon use changes during short-term osmotic, salinity, and cold stress in Arabidopsis thaliana. This could inform on the early mechanisms plants use to survive adverse environment, which is important for efficient agricultural production. We found that carbon allocation from source to sinks, and partitioning into major metabolite pools in the source leaf, sink leaves and roots showed both conserved and divergent responses to the stresses examined...
June 18, 2018: Scientific Reports
Jun Young Sonn, Jongbin Lee, Min Kyung Sung, Hwajung Ri, Jung Kyoon Choi, Chunghun Lim, Joonho Choe
Sleep and metabolism are physiologically and behaviorally intertwined; however, the molecular basis for their interaction remains poorly understood. Here, we identified a serine metabolic pathway as a key mediator for starvation-induced sleep suppression. Transcriptome analyses revealed that enzymes involved in serine biosynthesis were induced upon starvation in Drosophila melanogaster brains. Genetic mutants of astray ( aay ), a fly homolog of the rate-limiting phosphoserine phosphatase in serine biosynthesis, displayed reduced starvation-induced sleep suppression...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Boer Xie, Yuanyuan Wang, Drew R Jones, Kaushik Kumar Dey, Xusheng Wang, Yuxin Li, Ji-Hoon Cho, Timothy I Shaw, Haiyan Tan, Junmin Peng
High throughput untargeted metabolomics usually relies on complementary liquid chromatography-mass spectrometry (LC-MS) methods to expand the coverage of diverse metabolites, but the integration of those methods is not fully characterized. We systematically investigated the performance of hydrophilic interaction liquid chromatography (HILIC)-MS and nano-flow reverse phase liquid chromatography (nRPLC)-MS under 8 LC-MS settings, varying stationary phases (HILIC and C18), mobile phases (acidic and basic pH), and MS ionization modes (positive and negative)...
June 8, 2018: Analytical Chemistry
Diego Duchi, Abhishek Mazumder, Anssi M Malinen, Richard H Ebright, Achillefs N Kapanidis
RNA polymerase (RNAP) contains a mobile structural module, the 'clamp,' that forms one wall of the RNAP active-center cleft and that has been linked to crucial aspects of the transcription cycle, including promoter melting, transcription elongation complex stability, transcription pausing, and transcription termination. Using single-molecule FRET on surface-immobilized RNAP molecules, we show that the clamp in RNAP holoenzyme populates three distinct conformational states and interconvert between these states on the 0...
June 6, 2018: Nucleic Acids Research
Sofie V Hellsten, Rekha Tripathi, Mikaela M Ceder, Robert Fredriksson
Amino acid sensing and signaling is vital for cells, and both gene expression and protein levels of amino acid transporters are regulated in response to amino acid availability. Here, the aim was to study the regulation of all members of the SLC38 amino acid transporter family, Slc38a1-11 , in mouse brain cells following amino acid starvation. We reanalyzed microarray data for the immortalized hypothalamic cell line N25/2 subjected to complete amino acid starvation for 1, 2, 3, 5, or 16 h, focusing specifically on the SLC38 family...
2018: Frontiers in Molecular Biosciences
Mingxu Fang, Carl E Bauer
When faced with amino acid starvation, prokaryotic cells induce a stringent response that modulates their physiology. The stringent response is manifested by production of signaling molecules guanosine 5'-diphosphate,3'-diphosphate (ppGpp) and guanosine 5'-triphosphate,3'-diphosphate (pppGpp) that are also called alarmones. In many species, alarmone levels are regulated by a multidomain bifunctional alarmone synthetase/hydrolase called Rel. In this enzyme, there is an ACT domain at the carboxyl region that has an unknown function; however, similar ACT domains are present in other enzymes that have roles in controlling amino acid metabolism...
June 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Baehyun Shin, Roy Jung, Hyejin Oh, Gwen E Owens, Hyeongseok Lee, Seung Kwak, Ramee Lee, Susan L Cotman, Jong-Min Lee, Marcy E MacDonald, Ji-Joon Song, Ravi Vijayvargia, Ihn Sik Seong
The CAG repeat expansion that elongates the polyglutamine tract in huntingtin is the root genetic cause of Huntington's disease (HD), a debilitating neurodegenerative disorder. This seemingly slight change to the primary amino acid sequence alters the physical structure of the mutant protein and alters its activity. We have identified a set of G-quadruplex-forming DNA aptamers (MS1, MS2, MS3, MS4) that bind mutant huntingtin proximal to lysines K2932/K2934 in the C-terminal CTD-II domain. Aptamer binding to mutant huntingtin abrogated the enhanced polycomb repressive complex 2 (PRC2) stimulatory activity conferred by the expanded polyglutamine tract...
June 1, 2018: Molecular Therapy. Nucleic Acids
Yoshishige Kimura, Koji Tsutsumi, Alu Konno, Koji Ikegami, Saira Hameed, Tomomi Kaneko, Oktay Ismail Kaplan, Takayuki Teramoto, Manabi Fujiwara, Takeshi Ishihara, Oliver E Blacque, Mitsutoshi Setou
Glutamylation is a post-translational modification found on tubulin that can alter the interaction between microtubules (MTs) and associated proteins. The molecular mechanisms regulating tubulin glutamylation in response to the environment are not well understood. Here, we show that in the sensory cilia of Caenorhabditis elegans, tubulin glutamylation is upregulated in response to various signals such as temperature, osmolality, and dietary conditions. Similarly, tubulin glutamylation is modified in mammalian photoreceptor cells following light adaptation...
May 30, 2018: Scientific Reports
Jin Meng, Shawn M Ferguson
Folliculin (FLCN) is a tumor suppressor that coordinates cellular responses to changes in amino acid availability via regulation of the Rag guanosine triphosphatases. FLCN is recruited to lysosomes during amino acid starvation, where it interacts with RagA/B as a heterodimeric complex with FLCN-interacting proteins (FNIPs). The FLCN-FNIP heterodimer also has GTPase-activating protein (GAP) activity toward RagC/D. These properties raised two important questions. First, how is amino acid availability sensed to regulate lysosomal abundance of FLCN? Second, what is the relationship between FLCN lysosome localization, RagA/B interactions, and RagC/D GAP activity? In this study, we show that RagA/B nucleotide status determines the FLCN-FNIP1 recruitment to lysosomes...
May 30, 2018: Journal of Cell Biology
Toshiya Sakata, Akiko Saito, Haruyo Sugimoto
In this study, we report a novel method for the in situ measurement of autophagy under nutrient starvation using a principle of semiconductor technology. A semiconductor-based field-effect transistor (FET) biosensor enables the direct detection of ionic or molecular charges under biological conditions. In particular, cellular respiration accompanied by the generation of carbon dioxide can be continuously and directly monitored as a change in pH at a cell/sensor interface. When autophagy was induced in HeLa cells on a FET biosensor under nutrient starvation, the surface potential increased more significantly for about 15 h than that for nonstarved cells...
May 29, 2018: Scientific Reports
Ryo Murakami, Chingakham Ranjit Singh, Jacob Morris, Leiming Tang, Ian Harmon, Takasu Azuma, Tomohiro Miyoshi, Kosuke Ito, Katsura Asano, Toshio Uchiumi
Ribosomal stalk proteins recruit translation elongation GTPases to the factor-binding center of the ribosome. Initiation factor 5B (eIF5B in eukaryotes and aIF5B in archaea) is a universally conserved GTPase that promotes the joining of the large and small ribosomal subunits during translation initiation. Here we show that aIF5B binds to the C-terminal tail of the stalk protein. In the co-crystal structure, the interaction occurs between the hydrophobic amino acids of the stalk C-terminal tail and a small hydrophobic pocket on the surface of the GTP-binding domain (domain I) of aIF5B...
May 29, 2018: Molecular and Cellular Biology
Kevin M Mazor, Leiming Dong, Yuanhui Mao, Robert V Swanda, Shu-Bing Qian, Martha H Stipanuk
Although amino acids are known regulators of translation, the unique contributions of specific amino acids are not well understood. We compared effects of culturing HEK293T cells in medium lacking either leucine, methionine, histidine, or arginine on eIF2 and 4EBP1 phosphorylation and measures of mRNA translation. Methionine starvation caused the most drastic decrease in translation as assessed by polysome formation, ribosome profiling, and a measure of protein synthesis (puromycin-labeled polypeptides) but had no significant effect on eIF2 phosphorylation, 4EBP1 hyperphosphorylation or 4EBP1 binding to eIF4E...
May 24, 2018: Scientific Reports
Meriem Durgud, Saurabh Gupta, Ivan Ivanov, Amin Omidbakhshfard, Maria Benina, Saleh Alseekh, Nikola Staykov, Mareike Hauenstein, Paul Dijkwel, Stefan Hörtensteiner, Valentina Toneva, Yariv Brotman, Alisdair R Fernie, Bernd Mueller-Roeber, Tsanko Gechev
The desiccation-tolerant plant Haberlea rhodopensis can withstand months of darkness without any visible senescence. Here, we investigated the molecular mechanisms of this adaptation to prolonged (30 days) darkness and subsequent return to light. H. rhodopensis plants remained green and viable throughout the dark treatment. Transcriptomic analysis revealed that darkness regulated several transcription factor (TF) genes. Stress- and autophagy-related TFs such as ERF8, HSFA2b, RD26, TGA1, and WRKY33 were upregulated, while chloroplast- and flowering-related TFs such as ATH1, COL2, COL4, RL1, and PTAC7 were repressed...
May 22, 2018: Plant Physiology
Hirobumi Igawa, Akihiro Kikuchi, Hirofumi Misu, Kiyo-Aki Ishii, Shuichi Kaneko, Toshinari Takamura
AIMS/INTRODUCTION: Previous studies have shown that an organism's nutritional status changes the protein levels of insulin receptor substrate 1 (IRS-1) in a tissue-specific manner. Although the mechanisms underlying the regulation of IRS-1 in the nutrient-rich conditions associated with diabetes and insulin resistance have been well studied, those under nutrient-poor conditions remain unknown. The aim of the present study was to investigate how IRS-1 protein levels change depending on the nutritional status of 3T3-L1 preadipocytes...
May 22, 2018: Journal of Diabetes Investigation
Simone C Vitor, Luciano do Amarante, Ladaslav Sodek
A substantial increase in malate in the xylem sap of soybean subjected to mineral N starvation originates mainly from aspartate, a prominent amino acid of the phloem. A substantial increase in xylem malate was found when non-nodulated soybean plants were transferred to a N-free medium. Nodulated plants growing in the absence of mineral N and, therefore, dependent on symbiotic N2 fixation also contained elevated concentrations of malate in the xylem sap. When either nitrate or ammonium was supplied, malate concentrations in the xylem sap were low, both for nodulated and non-nodulated plants...
May 16, 2018: Planta
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