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https://www.readbyqxmd.com/read/28069741/tor-complex-2-regulated-protein-kinase-fpk1-stimulates-endocytosis-via-inhibition-of-ark1-prk1-related-protein-kinase-akl1-in-saccharomyces-cerevisiae
#1
Françoise M Roelants, Kristin L Leskoske, Ross T A Pedersen, Alexander Muir, Jeffrey M-H Liu, Gregory C Finnigan, Jeremy Thorner
Depending on the stress, plasma membrane alterations activate or inhibit yeast Target of Rapamycin (TOR) Complex 2, which, in turn, upregulates or downregulates the activity of its essential downstream effector, protein kinase Ypk1. Through phosphorylation of multiple substrates, Ypk1 controls many processes that restore homeostasis. One such substrate is protein kinase Fpk1, which is negatively regulated by Ypk1. Fpk1 phosphorylates and stimulates flippases that translocate aminoglycerophospholipids from the outer to the inner leaflet of the plasma membrane...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28061020/a-p4-atpase-subunit-of-the-cdc50-family-plays-a-role-in-iron-acquisition-and-virulence-in-cryptococcus-neoformans
#2
Guanggan Hu, Mélissa Caza, Erik Bakkeren, Matthias Kretschmer, Gaurav Bairwa, Ethan Reiner, James Kronstad
The pathogenic fungus Cryptococcus neoformans delivers virulence factors such as capsule polysaccharide to the cell surface to cause disease in vertebrate hosts. In this study, we screened for mutants sensitive to the secretion inhibitor brefeldin A to identify secretory pathway components that contribute to virulence. We identified an ortholog of the Cdc50 family of the non-catalytic subunit of type IV P-type ATPases (flippases) that establish phospholipid asymmetry in membranes and function in vesicle-mediated trafficking...
January 6, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28057802/cfs1p-a-novel-membrane-protein-in-the-pq-loop-family-is-involved-in-phospholipid-flippase-functions-in-yeast
#3
Takaharu Yamamoto, Konomi Fujimura-Kamada, Eno Shioji, Risa Suzuki, Kazuma Tanaka
Type 4 P-type ATPases (P4-ATPases) function as phospholipid flippases, which translocate phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of the lipid bilayer, to generate and maintain asymmetric distribution of phospholipids at the plasma membrane and endosomal/Golgi membranes. The budding yeast Saccharomyces cerevisiae has four heteromeric flippases (Drs2p, Dnf1p, Dnf2p, and Dnf3p), associated with the Cdc50p family noncatalytic subunit, and one monomeric flippase, Neo1p They have been suggested to function in vesicle formation in membrane trafficking pathways, but details of their mechanisms remain to be clarified...
January 5, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28034798/phospholipid-flippases-dnfa-and-dnfb-exhibit-differential-dynamics-within-the-a-nidulans-spitzenk%C3%A3-rper
#4
Zachary Schultzhaus, Wenhui Zheng, Zonghua Wang, Rosa Mouriño-Pérez, Brian Shaw
The Spitzenkörper is a structure at the apex of growing cells in many filamentous fungi. Ultrastructural studies indicate that the Spitzenkörper is an organized mass of secretory vesicles, with different types of vesicles present in outer and inner layers. Here, we used live-cell imaging to demonstrate that the phospholipid flippases DnfA and DnfB, which preferentially localize to the outer and inner layers, respectively, exhibit different dynamics in the Spitzenkörper of Aspergillus nidulans. Additionally, deletion of dnfA partially destabilized the Spitzenkörper, while the depletion of cdc50, an essential β-subunit of most flippases, had dramatic effects on hyphal tip organization and morphology...
December 26, 2016: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28024149/crystal-structure-of-the-mop-flippase-murj-in-an-inward-facing-conformation
#5
Alvin C Y Kuk, Ellene H Mashalidis, Seok-Yong Lee
Peptidoglycan (PG) protects bacteria from osmotic lysis, and its biogenesis is a key antibiotic target. A central step in PG biosynthesis is flipping of the lipid-linked PG precursor lipid II across the cytoplasmic membrane for subsequent incorporation into PG. MurJ, part of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) transporter superfamily, was recently shown to carry out this process. However, understanding of how MurJ flips lipid II, and of how MOP transporters operate in general, remains limited due to a lack of structural information...
December 26, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28004795/coupled-atpase-adenylate-kinase-activity-in-abc-transporters
#6
Hundeep Kaur, Andrea Lakatos-Karoly, Ramona Vogel, Anne Nöll, Robert Tampé, Clemens Glaubitz
ATP-binding cassette (ABC) transporters, a superfamily of integral membrane proteins, catalyse the translocation of substrates across the cellular membrane by ATP hydrolysis. Here we demonstrate by nucleotide turnover and binding studies based on (31)P solid-state NMR spectroscopy that the ABC exporter and lipid A flippase MsbA can couple ATP hydrolysis to an adenylate kinase activity, where ADP is converted into AMP and ATP. Single-point mutations reveal that both ATPase and adenylate kinase mechanisms are associated with the same conserved motifs of the nucleotide-binding domain...
December 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27959517/the-ins-and-outs-of-lipid-flip-flop
#7
John S Allhusen, John C Conboy
Our current view of cellular membranes centers on the fluid-mosaic model, which envisions the cellular membrane as a "liquidlike" bilayer of lipids, cholesterol, and proteins that freely diffuse in two dimensions. In stark contrast, the exchange of materials between the leaflets of a bilayer was presumed to be prohibited by the large enthalpic barrier associated with translocating hydrophilic materials, such as a charged lipid headgroup, through the hydrophobic membrane core. This static picture with regard to lipid translocation (or "flip-flop" as it is affectionately known) has been a long-held belief in the study of membrane dynamics...
December 13, 2016: Accounts of Chemical Research
https://www.readbyqxmd.com/read/27956138/biogenesis-transport-and-remodeling-of-lysophospholipids-in-gram-negative-bacteria
#8
REVIEW
Lei Zheng, Yibin Lin, Shuo Lu, Jiazhe Zhang, Mikhail Bogdanov
Lysophospholipids (LPLs) are metabolic intermediates in bacterial phospholipid turnover. Distinct from their diacyl counterparts, these inverted cone-shaped molecules share physical characteristics of detergents, enabling modification of local membrane properties such as curvature. The functions of LPLs as cellular growth factors or potent lipid mediators have been extensively demonstrated in eukaryotic cells but are still undefined in bacteria. In the envelope of Gram-negative bacteria, LPLs are derived from multiple endogenous and exogenous sources...
December 9, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27932490/c-terminus-of-the-p4-atpase-atp8a2-functions-in-protein-folding-and-regulation-of-phospholipid-flippase-activity
#9
Madhavan Chalat, Kody Moleschi, Robert S Molday
ATP8A2 is a P4-ATPase that flips phosphatidylserine and phosphatidylethanolamine across cell membranes. This generates membrane phospholipid asymmetry, a property important in many cellular processes including vesicle trafficking. ATP8A2 deficiency causes severe neurodegenerative diseases. We have investigated the role of the C-terminus of ATP8A2 in its expression, subcellular localization, interaction with its subunit CDC50A, and function as a phosphatidylserine flippase. C-terminal deletion mutants exhibited a reduced tendency to solubilize in mild detergent and exit the endoplasmic reticulum...
December 8, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27871883/importance-of-phosphatidylcholine-on-the-chloroplast-surface
#10
REVIEW
César Botella, Juliette Jouhet, Maryse A Block
In plant cells, phosphatidylcholine (PC) is a major glycerolipid of most membranes but practically lacking from the plastid internal membranes. In chloroplasts, PC is absent from the thylakoids and the inner envelope membrane. It is however the main component of the outer envelope membrane, where it exclusively distributes in the outer monolayer. This unique distribution is likely related with operational compartmentalization of plant lipid metabolism. In this review, we summarize the different mechanisms involved in homeostasis of PC in plant cells...
January 2017: Progress in Lipid Research
https://www.readbyqxmd.com/read/27825076/phospholipid-flippase-activities-and-substrate-specificities-of-human-type-iv-p-type-atpases-localized-to-the-plasma-membrane
#11
Hiroyuki Takatsu, Gaku Tanaka, Katsumori Segawa, Jun Suzuki, Shigekazu Nagata, Kazuhisa Nakayama, Hye-Won Shin
No abstract text is available yet for this article.
October 7, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27771709/novel-insights-in-the-regulation-of-phosphatidylserine-exposure-in-human-red-blood-cells
#12
Mauro C Wesseling, Lisa Wagner-Britz, Duc Bach Nguyen, Salome Asanidze, Judy Mutua, Nagla Mohamed, Benjamin Hanf, Mehrdad Ghashghaeinia, Lars Kaestner, Ingolf Bernhardt
BACKGROUND/AIMS: In previous publications we were able to demonstrate the exposure of phosphatidylserine (PS) in the outer membrane leaflet after activation of red blood cells (RBCs) by lysophosphatidic acid (LPA), phorbol-12 myristate-13acetate (PMA), or 4-bromo-A23187 (A23187). It has been concluded that three different mechanisms are responsible for the PS exposure in human RBCs: (i) Ca2+-stimulated scramblase activation (and flippase inhibition) by A23187, LPA, and PMA; (ii) PKCα activation by LPA and PMA; and (iii) enhanced lipid flip flop caused by LPA...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27748750/discovery-of-mrsa-active-antibiotics-using-primary-sequence-from-the-human-microbiome
#13
John Chu, Xavier Vila-Farres, Daigo Inoyama, Melinda Ternei, Louis J Cohen, Emma A Gordon, Boojala Vijay B Reddy, Zachary Charlop-Powers, Henry A Zebroski, Ricardo Gallardo-Macias, Mark Jaskowski, Shruthi Satish, Steven Park, David S Perlin, Joel S Freundlich, Sean F Brady
Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When we applied the approach to nonribosomal peptide synthetase gene clusters from human-associated bacteria, we identified the humimycins. These antibiotics inhibit lipid II flippase and potentiate β-lactam activity against methicillin-resistant Staphylococcus aureus in mice, potentially providing a new treatment regimen...
December 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27738552/neo1-and-phosphatidylethanolamine-contribute-to-vacuole-membrane-fusion-in-saccharomyces-cerevisiae
#14
Yuantai Wu, Mehmet Takar, Andrea A Cuentas-Condori, Todd R Graham
NEO1 is an essential gene in budding yeast and belongs to a highly conserved subfamily of P-type ATPase genes that encode phospholipid flippases. Inactivation of temperature sensitive neo1(ts) alleles produces pleiomorphic defects in the secretory and endocytic pathways, including fragmented vacuoles. A screen for multicopy suppressors of neo1-2(ts) growth defects yielded YPT7, which encodes a Rab7 homolog involved in SNARE-dependent vacuolar fusion. YPT7 suppressed the vacuole fragmentation phenotype of neo1-2, but did not suppress Golgi-associated protein trafficking defects...
July 2016: Cellular Logistics
https://www.readbyqxmd.com/read/27733620/the-phospholipid-flippase-atp9a-is-required-for-the-recycling-pathway-from-the-endosomes-to-the-plasma-membrane
#15
Yoshiki Tanaka, Natsuki Ono, Takahiro Shima, Gaku Tanaka, Yohei Katoh, Kazuhisa Nakayama, Hiroyuki Takatsu, Hye-Won Shin
Type IV P-type ATPases (P4-ATPases) are phospholipid flippases that translocate phospholipids from the exoplasmic (or luminal) to the cytoplasmic leaflet of lipid bilayers. In Saccharomyces cerevisiae, P4-ATPases are localized to specific subcellular compartments and play roles in compartment-mediated membrane trafficking; however, roles of mammalian P4-ATPases in membrane trafficking are poorly understood. We previously reported that ATP9A, one of 14 human P4-ATPases, is localized to endosomal compartments and the Golgi complex...
December 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27696908/decoding-p4-atpase-substrate-interactions
#16
Bartholomew P Roland, Todd R Graham
Cellular membranes display a diversity of functions that are conferred by the unique composition and organization of their proteins and lipids. One important aspect of lipid organization is the asymmetric distribution of phospholipids (PLs) across the plasma membrane. The unequal distribution of key PLs between the cytofacial and exofacial leaflets of the bilayer creates physical surface tension that can be used to bend the membrane; and like Ca(2+), a chemical gradient that can be used to transduce biochemical signals...
October 4, 2016: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27696669/mutant-analysis-by-rescue-gene-excision-new-tools-for-mosaic-studies-in-drosophila
#17
Qingxiang Zhou, Scott J Neal, Francesca Pignoni
A host of classical and molecular genetic tools make Drosophila a tremendous model for the dissection of gene activity. In particular, the FLP-FRT technique for mitotic recombination has greatly enhanced gene loss-of-function analysis. This technique efficiently induces formation of homozygous mutant clones in tissues of heterozygous organisms. However, the dependence of the FLP-FRT method on cell division, and other constraints, also impose limits on its effectiveness. We describe here the generation and testing of tools for Mutant Analysis by Rescue Gene Excision (MARGE), an approach whereby mutant cells are formed by loss of a rescue transgene in a homozygous mutant organism...
November 2016: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/27649050/phospholipids-how-to-flip-a-flippase
#18
Caitlin Deane
No abstract text is available yet for this article.
September 20, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27628304/phospholipid-flippases-attenuate-lps-induced-tlr4-signaling-by-mediating-endocytic-retrieval-of-toll-like-receptor-4
#19
Vincent A van der Mark, Mohammed Ghiboub, Casper Marsman, Jing Zhao, Remco van Dijk, Johan K Hiralall, Kam S Ho-Mok, Zoë Castricum, Wouter J de Jonge, Ronald P J Oude Elferink, Coen C Paulusma
P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-κB activation...
September 14, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27537185/the-o-antigen-flippase-wzk-can-substitute-for-murj-in-peptidoglycan-synthesis-in-helicobacter-pylori-and-escherichia-coli
#20
Wael Elhenawy, Rebecca M Davis, Jutta Fero, Nina R Salama, Mario F Felman, Natividad Ruiz
The peptidoglycan (PG) cell wall is an essential component of the cell envelope of most bacteria. Biogenesis of PG involves a lipid-linked disaccharide-pentapeptide intermediate called lipid II, which must be translocated across the cytoplasmic membrane after it is synthesized in the inner leaflet of this bilayer. Accordingly, it has been demonstrated that MurJ, the proposed lipid II flippase in Escherichia coli, is required for PG biogenesis, and thereby viability. In contrast, MurJ is not essential in Bacillus subtilis because this bacterium produces AmJ, an unrelated protein that is functionally redundant with MurJ...
2016: PloS One
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