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https://www.readbyqxmd.com/read/29674454/control-of-vacuole-membrane-homeostasis-by-a-resident-pi-3-5-kinase-inhibitor
#1
P C Malia, Johannes Numrich, Taki Nishimura, Ayelén González Montoro, Christopher J Stefan, Christian Ungermann
Lysosomes have an important role in cellular protein and organelle quality control, metabolism, and signaling. On the surface of lysosomes, the PIKfyve/Fab1 complex generates phosphatidylinositol 3,5-bisphosphate, PI-3,5-P2 , which is critical for lysosomal membrane homeostasis during acute osmotic stress and for lysosomal signaling. Here, we identify the inverted BAR protein Ivy1 as an inhibitor of the Fab1 complex with a direct influence on PI-3,5-P2 levels and vacuole homeostasis. Ivy1 requires Ypt7 binding for its function, binds PI-3,5-P2 , and interacts with the Fab1 kinase...
May 1, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29449881/a-copper-controlled-rna-interference-system-for-reversible-silencing-of-target-genes-in-trichoderma-reesei
#2
Lei Wang, Fanglin Zheng, Weixin Zhang, Yaohua Zhong, Guanjun Chen, Xiangfeng Meng, Weifeng Liu
Background: Trichoderma reesei is a primary lignocellulosic enzyme producer in industry. However, the mechanisms underlying cellulase synthesis as well as other physiological processes are insufficiently understood partly due to the sophisticated process for its genetic manipulation. Target gene knockdown by RNA interference (RNAi) is a powerful tool for genetic research and biotechnology in eukaryotes including filamentous fungi. Previously reported RNAi system in T. reesei was either uncontrollable or only applicable in certain nutrition state...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28637746/early-protection-to-stress-mediated-by-cdk-dependent-pi3-5p-2-signaling-from-the-vacuole-lysosome
#3
Natsuko Jin, Yui Jin, Lois S Weisman
Adaptation to environmental stress is critical for cell survival. Adaptation generally occurs via changes in transcription and translation. However, there is a time lag before changes in gene expression, which suggests that more rapid mechanisms likely exist. In this study, we show that in yeast, the cyclin-dependent kinase Pho85/CDK5 provides protection against hyperosmotic stress and acts before long-term adaptation provided by Hog1. This protection requires the vacuolar/endolysosomal signaling lipid PI3,5P2 We show that Pho85/CDK5 directly phosphorylates and positively regulates the PI3P-5 kinase Fab1/PIKfyve complex and provide evidence that this regulation is conserved in mammalian cells...
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28463007/bio-orthogonal-cross-linking-chemistry-enables-in-situ-protein-encapsulation-and-provides-sustained-release-from-hyaluronic-acid-based-hydrogels
#4
Amin Famili, Karthikan Rajagopal
Chemically cross-linked hydrogels are promising systems for protein delivery applications, but their utility may be limited due to the possibility of protein reaction with hydrogel precursors. Herein, a catalyst-free inverse-demand Diels-Alder reaction between tetrazine and norbornene groups was used to demonstrate the bio-orthogonal nature of cross-linking chemistry that is chemically inert to proteins. Tetrazine-modified hyaluronic acid and norbornene-modified polyethylene glycol were used as hydrogel precursors for in situ encapsulation of a model protein, Fab1...
June 5, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28302928/pi5p-and-pi-3-5-p-2-minor-but-essential-phosphoinositides
#5
REVIEW
Junya Hasegawa, Bethany S Strunk, Lois S Weisman
In most eukaryotes, phosphoinositides (PIs) have crucial roles in multiple cellular functions. Although the cellular levels of phosphatidylinositol 5-phosphate (PI5P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2 ) are extremely low relative to some other PIs, emerging evidence demonstrates that both lipids are crucial for the endocytic pathway, intracellular signaling, and adaptation to stress. Mutations that causes defects in the biosynthesis of PI5P and PI(3,5)P2 are linked to human diseases including neurodegenerative disorders...
May 3, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28292259/genome-wide-association-mapping-and-identification-of-candidate-genes-for-fatty-acid-composition-in-brassica-napus-l-using-snp-markers
#6
Cunmin Qu, Ledong Jia, Fuyou Fu, Huiyan Zhao, Kun Lu, Lijuan Wei, Xinfu Xu, Ying Liang, Shimeng Li, Rui Wang, Jiana Li
BACKGROUND: B. napus (oilseed) is an important source of edible vegetable oil, and its nutritional and economic value is determined by its fatty acid composition and content. RESULTS: Using the Brassica 60 K SNP array, we performed a genome-wide association study of fatty acid composition in a population of 520 genetically diverse oilseed accessions. Using the PCA + K model in TASSEL 5.2.1, we identified 62 genomic regions that were significantly associated with the composition of seven fatty acids, and five consensus regions that mapped to the A2, A8, A9, C1, and C3 chromosomes, respectively, of the Brassica napus Darmor-bzh genome...
March 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28273166/ste12-fab1-phosphatidylinositol-3-phosphate-5-kinase-is-required-for-nitrogen-regulated-mitotic-commitment-and-cell-size-control
#7
David Cobley, Lenka Hálová, Marie Schauries, Adrian Kaczmarek, Mirita Franz-Wachtel, Wei Du, Karsten Krug, Boris Maček, Janni Petersen
Tight coupling of cell growth and cell cycle progression enable cells to adjust their rate of division, and therefore size, to the demands of proliferation in varying nutritional environments. Nutrient stress promotes inhibition of Target Of Rapamycin Complex 1 (TORC1) activity. In fission yeast, reduced TORC1 activity advances mitotic onset and switches growth to a sustained proliferation at reduced cell size. A screen for mutants, that failed to advance mitosis upon nitrogen stress, identified a mutant in the PIKFYVE 1-phosphatidylinositol-3-phosphate 5-kinase fission yeast homolog Ste12...
2017: PloS One
https://www.readbyqxmd.com/read/28158631/visualization-of-phosphatidylinositol-3-5-bisphosphate-dynamics-by-a-tandem-ml1n-based-fluorescent-protein-probe-in-arabidopsis
#8
Tomoko Hirano, Kelly Stecker, Teun Munnik, Haoxing Xu, Masa H Sato
Phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is a low-abundance phospholipid known to be associated with a wide variety of physiological functions in plants. However, the localization and dynamics of PI(3,5)P2 in plant cells remain largely unknown, partially due to the lack of an effective fluorescent probe. Using Arabidopsis transgenic plant expressing the PI(3,5)P2-labeling fluorescent probe (tagRFP-ML1N*2) developed based on a tandem repeat of the cytosolic phosphoinositide-interacting domain (ML1N) of the mammalian lysosomal transient receptor potential cation channel, Mucolipin 1 (TRPML1), here we show that PI(3,5)P2 is predominantly localized on the limited membranes of the FAB1- and SNX1-positive late endosomes, but rarely localized on the membranes of plant vacuoles or trans-Golgi network/early endosomes of cortical cells of the root differentiation zone...
July 1, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28148651/an-intramolecular-interaction-within-the-lipid-kinase-fab1-regulates-cellular-phosphatidylinositol-3-5-bisphosphate-lipid-levels
#9
Michael J Lang, Bethany S Strunk, Nadia Azad, Jason L Petersen, Lois S Weisman
Phosphorylated phosphoinositide lipids (PPIs) are low-abundance signaling molecules that control signal transduction pathways and are necessary for cellular homeostasis. The PPI phosphatidylinositol (3,5)-bisphosphate (PI(3,5)P2 ) is essential in multiple organ systems. PI(3,5)P2 is generated from PI3P by the conserved lipid kinase Fab1/PIKfyve. Defects in the dynamic regulation of PI(3,5)P2 are linked to human diseases. However, few mechanisms that regulate PI(3,5)P2 have been identified. Here we report an intramolecular interaction between the yeast Fab1 kinase region and an upstream conserved cysteine-rich (CCR) domain...
April 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27803131/inhibition-of-phosphatidylinositol-3-5-bisphosphate-production-has-pleiotropic-effects-on-various-membrane-trafficking-routes-in-arabidopsis
#10
Tomoko Hirano, Teun Munnik, Masa H Sato
Phosphoinositides play an important role in various membrane trafficking events in eukaryotes. One of them, however, phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], has not been studied widely in plants. Using a combination of fluorescent reporter proteins and the PI(3,5)P2-specific inhibitor YM202636, here we demonstrated that in Arabidopsis thaliana, PI(3,5)P2 affects various membrane trafficking events, mostly in the post-Golgi routes. We found that YM201636 treatment effectively reduced PI(3,5)P2 concentration not only in the wild type but also in FAB1A-overexpressing Arabidopsis plants...
January 1, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/27701906/escrts-and-associated-proteins-in-lysosomal-fusion-with-endosomes-and-autophagosomes
#11
Priyanka Majumder, Oishee Chakrabarti
Endolysosomal and autophagosomal degradation pathways are highly connected at various levels, sharing multiple molecular effectors that modulate them individually or simultaneously. These two lysosomal degradative pathways are primarily involved in the disposal of cargo internalized from the cell surface or long-lived proteins or aggregates and aged organelles present in the cytosol. Both of these pathways involve a number of carefully regulated vesicular fusion events that are dependent on ESCRT proteins. The ESCRT proteins especially ESCRT-I and III participate in the regulation of fusion events between autophagosome/amphisome and lysosome...
July 22, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/27310477/proteomics-for-drug-resistance-on-the-food-chain-multidrug-resistant-escherichia-coli-proteomes-from-slaughtered-pigs
#12
Sónia Ramos, Nuno Silva, Michel Hébraud, Hugo M Santos, Júlio Dinis Nunes-Miranda, Luís Pinto, José E Pereira, José-Luis Capelo, Patrícia Poeta, Gilberto Igrejas
Understanding global drug resistance demands an integrated vision, focusing on both human and veterinary medicine. Omics technologies offer new vistas to decipher mechanisms of drug resistance in the food chain. For example, Escherichia coli resistance to major antibiotics is increasing whereas multidrug resistance (MDR) strains are now commonly found in humans and animals. Little is known about the structural and metabolic changes in the cell that trigger resistance to antimicrobial agents. Proteomics is an emerging field that is used to advance our knowledge in global health and drug resistance in the food chain...
June 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/26934981/a-cell-permeable-tool-for-analysing-app-intracellular-domain-function-and-manipulation-of-pikfyve-activity
#13
Benjamin Guscott, Zita Balklava, Stephen T Safrany, Thomas Wassmer
The mechanisms for regulating PIKfyve complex activity are currently emerging. The PIKfyve complex, consisting of the phosphoinositide kinase PIKfyve (also known as FAB1), VAC14 and FIG4, is required for the production of phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2]. PIKfyve function is required for homoeostasis of the endo/lysosomal system and is crucially implicated in neuronal function and integrity, as loss of function mutations in the PIKfyve complex lead to neurodegeneration in mouse models and human patients...
2016: Bioscience Reports
https://www.readbyqxmd.com/read/26862203/phosphatidylinositol-3-5-bisphosphate-regulation-of-cellular-events-in-space-and-time
#14
REVIEW
Natsuko Jin, Michael J Lang, Lois S Weisman
Phosphorylated phosphatidylinositol lipids are crucial for most eukaryotes and have diverse cellular functions. The low-abundance signalling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is critical for cellular homoeostasis and adaptation to stimuli. A large complex of proteins that includes the lipid kinase Fab1-PIKfyve, dynamically regulates the levels of PI(3,5)P2. Deficiencies in PI(3,5)P2 are linked to some human diseases, especially those of the nervous system. Future studies will probably determine new, undiscovered regulatory roles of PI(3,5)P2, as well as uncover mechanistic insights into how PI(3,5)P2 contributes to normal human physiology...
February 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/26662798/fig4-regulates-lysosome-membrane-homeostasis-independent-of-phosphatase-function
#15
Rajnish Bharadwaj, Kathleen M Cunningham, Ke Zhang, Thomas E Lloyd
FIG4 is a phosphoinositide phosphatase that is mutated in several diseases including Charcot-Marie-Tooth Disease 4J (CMT4J) and Yunis-Varon syndrome (YVS). To investigate the mechanism of disease pathogenesis, we generated Drosophila models of FIG4-related diseases. Fig4 null mutant animals are viable but exhibit marked enlargement of the lysosomal compartment in muscle cells and neurons, accompanied by an age-related decline in flight ability. Transgenic animals expressing Drosophila Fig4 missense mutations corresponding to human pathogenic mutations can partially rescue lysosomal expansion phenotypes, consistent with these mutations causing decreased FIG4 function...
February 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/26515455/overexpression-of-fab1a-gfp-recruits-snx2b-on-the-endosome-membrane-in-snx1-1-mutant-in-arabidopsis
#16
Tomoko Hirano, Masa H Sato
Phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is one of the phosphoinositides that controls endosomal trafficking events in eukaryotes. PtdIns(3,5)P2 is produced from PI(3)P by phosphatidylinositol 3-phosphate 5-kinase FAB1/PIKfyve. Recently, we reported that FAB1 predominantly localizes on the SNX1-residing late endosomes and a loss-of FAB1 function causes the release of late endosomal effector proteins, ARA7/RABF2b and SORTING NEXIN 1 from the endosome membrane, indicating that FAB1 or its product PtdIns(3,5)P2 mediates the maturation process of the late endosomes...
2016: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/26353760/phosphatidylinositol-3-phosphate-5-kinase-fab1-pikfyve-kinase-mediates-endosome-maturation-to-establish-endosome-cortical-microtubule-interaction-in-arabidopsis
#17
Tomoko Hirano, Teun Munnik, Masa H Sato
Phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] is an important lipid in membrane trafficking in animal and yeast systems; however, its role is still largely obscure in plants. Here, we demonstrate that the phosphatidylinositol 3-phosphate 5-kinase, formation of aploid and binucleate cells1 (FAB1)/FYVE finger-containing phosphoinositide kinase (PIKfyve), and its product, PtdIns(3,5)P2, are essential for the maturation process of endosomes to mediate cortical microtubule association of endosomes, thereby controlling proper PIN-FORMED protein trafficking in young cortical and stele cells of root...
November 2015: Plant Physiology
https://www.readbyqxmd.com/read/26224803/mutations-in-the-prokaryotic-pathway-rescue-the-fatty-acid-biosynthesis1-mutant-in-the-cold
#18
Jinpeng Gao, James G Wallis, John Browse
The Arabidopsis (Arabidopsis thaliana) fatty acid biosynthesis1 (fab1) mutant has increased levels of the saturated fatty acid 16:0 due to decreased activity of 3-ketoacyl-acyl carrier protein (ACP) synthase II. In fab1 leaves, phosphatidylglycerol, the major chloroplast phospholipid, contains up to 45% high-melting-point molecular species (molecules that contain only 16:0, 16:1-trans, and 18:0), a trait associated with chilling-sensitive plants, compared with less than 10% in wild-type Arabidopsis. Although they do not exhibit typical chilling sensitivity, when exposed to low temperatures (2°C-6°C) for long periods, fab1 plants do suffer collapse of photosynthesis, degradation of chloroplasts, and eventually death...
September 2015: Plant Physiology
https://www.readbyqxmd.com/read/26099467/investigation-of-fragment-antibody-stability-and-its-release-mechanism-from-poly-lactide-co-glycolide-triacetin-depots-for-sustained-release-applications
#19
Debby P Chang, Vivek Kumar Garripelli, Jennifer Rea, Robert Kelley, Karthikan Rajagopal
Achieving long-term drug release from polymer-based delivery systems continues to be a challenge particularly for the delivery of large hydrophilic molecules such as therapeutic antibodies and proteins. Here, we report on the utility of an in situ-forming and injectable polymer-solvent system for the long-term release of a model antibody fragment (Fab1). The delivery system was prepared by dispersing a spray-dried powder of Fab1 within poly(lactide-co-glycolide) (PLGA)-triacetin solution. The formulation viscosity was within the range 1...
October 2015: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/25803831/atg18-and-fab1-are-involved-in-dehydration-stress-tolerance-in-saccharomyces-cerevisiae
#20
Gema López-Martínez, Mar Margalef-Català, Francisco Salinas, Gianni Liti, Ricardo Cordero-Otero
Recently, different dehydration-based technologies have been evaluated for the purpose of cell and tissue preservation. Although some early results have been promising, they have not satisfied the requirements for large-scale applications. The long experience of using quantitative trait loci (QTLs) with the yeast Saccharomyces cerevisiae has proven to be a good model organism for studying the link between complex phenotypes and DNA variations. Here, we use QTL analysis as a tool for identifying the specific yeast traits involved in dehydration stress tolerance...
2015: PloS One
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