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Phosphatidic acid

Yanhui Yu, Na Zhao, Jiaqi An, Xichen Zhang
Autophagy is a main defense strategy by which infected host cells can virtually induce the killing of parasite, including Toxoplasma gondii. However, the regulatory mechanisms of autophagy in T. gondii-infected nonhematopoietic cells are still unknown. Emerging evidence indicates that CCAAT/enhancer-binding protein β (C/EBP β) is associated with the regulation of autophagy. Herein, we hypothesized that C/EBP β plays roles in inducing autophagy in nonhematopoietic cells. Expression of C/EBP β was aberrantly regulated in endothelial cells and retinal pigment epithelial cells challenged by T...
January 16, 2017: DNA and Cell Biology
Péter Várnai, Gergő Gulyás, Dániel J Tóth, Mira Sohn, Nivedita Sengupta, Tamas Balla
One of the largest challenges in cell biology is to map the lipid composition of the membranes of various organelles and define the exact location of processes that control the synthesis and distribution of lipids between cellular compartments. The critical role of phosphoinositides, low-abundant lipids with rapid metabolism and exceptional regulatory importance in the control of almost all aspects of cellular functions created the need for tools to visualize their localizations and dynamics at the single cell level...
December 31, 2016: Cell Calcium
L W R Tay, Z Wang, G Du
Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a lipid second messenger that regulates a wide array of essential cellular events, such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, adhesion, and motility. To control the spatiotemporal production of PI(4,5)P2, the activity of type 1 phosphotidylinositol-4-phosphate-5-kinases (PIPKIs) is tightly regulated by small GTPases and another signaling lipid, phosphatidic acid (PA). It is of interest that PI(4,5)P2 is also a critical cofactor for the activation of the PA-generating enzyme, phospholipase D (PLD)...
2017: Methods in Enzymology
J Gomez-Cambronero, A J Morris, K M Henkels
We describe methods for studying phospholipase D (PLD) interactions with signaling proteins and modulation of these interactions by the PLD reaction product, phosphatidic acid (PA). PLD is fundamental to the physiological maintenance of cellular/intracellular membranes, protein trafficking, cytoskeletal dynamics, membrane remodeling, cell proliferation, meiotic division and sporulation. PA is an acidic phospholipid involved in the biosynthesis of many other lipids that affects the enzymatic activities of many different signaling proteins via protein-lipid interactions or as a substrate...
2017: Methods in Enzymology
F Philip, E E Ha, M A Seeliger, M A Frohman
The phospholipase D (PLD) enzymatic superfamily regulates a wide range of cell biological and physiological pathways, including platelet activation, immune responses, cancer, and spermatogenesis. The three main enzymatic actions of the superfamily entail (i) hydrolyzing membrane phospholipids (phosphatidylcholine (PC) and cardiolipin) to generate choline and the second messenger signaling lipid phosphatidic acid (PA), (ii) using ethanol to transphosphatidylate PC to generate the long-lived metabolite phosphatidylethanol, and (iii) hydrolyzing RNA transcripts to generate piRNAs, the third form of endogenous RNAi...
2017: Methods in Enzymology
André Hädicke, Alfred Blume
Differential Scanning Calorimetry (DSC) and Fourier transformed Infrared (FT-IR) spectroscopy were used to test the influence of acyl chain length, acyl chain saturation, and chemical structure of anionic phospholipids on the interaction with cationic model peptides (KX)4K, with amino acid X=A, Abu, and L. The lipids used were phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidic acid (PA), and cardiolipin (CL). DSC was used to monitor the phase transition of lipid vesicles before and after peptide binding...
December 26, 2016: Biochimica et Biophysica Acta
Shaoxing Chen, Yao Xu, Li-Xia Ke
A novel extremely halophilic archaeon, strain Y73T was isolated from a salt mine in Yunnan, China. Colonies formed on solid medium were circular (2-3 mm in diameter) with smooth, orange, glistening and convex (~1 mm in elevation). Cells were Gram-stain-negative, non-motile and pleomorphic. Mg2+ was required for growth (optimum at 0.05 M). Optimal growth was observed at 20 % (w/v) NaCl, 42-45 °C and pH 7.5-8.5 in aerobic conditions. The result of sequence similarity searching of 16S rRNA gene showed that strain Y73T was closely related to Halorubrum halophilum B8T (identity: 98...
December 29, 2016: International Journal of Systematic and Evolutionary Microbiology
Harold J G Meijer, John A J van Himbergen, Alan Musgrave, Teun Munnik
Osmotic stress rapidly activates several phospholipid signalling pathways in the unicellular alga Chlamydomonas. In this report, we have studied the effects of salt-acclimation on growth and phospholipid signalling. Growing cells on media containing 100 mM NaCl increased their salt-tolerance but did not affect the overall phospholipid content, except that levels of phosphatidylinositol phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] were reduced by one-third. When these NaCl-acclimated cells were treated with increasing concentrations of salt, the same lipid signalling pathways as in non-acclimated cells were activated...
December 22, 2016: Phytochemistry
Xiuhong Zhai, Yong-Guang Gao, Shrawan K Mishra, Dhirendra K Simanshu, Ivan A Boldyrev, Linda M Benson, H Robert Bergen, Lucy Malinina, John Mundy, Julian G Molotkovsky, Dinshaw J Patel, Rhoderick E Brown
Genetic models for studying localized cell suicide that halt the spread of pathogen infection and immune response activation in plants include Arabidopsis accelerated-cell-death11 (acd11) In this mutant, sphingolipid homeostasis is disrupted via depletion of ACD11, a lipid transfer protein that is specific for ceramide-1-phosphate (C1P) and phyto-C1P. The C1P binding site in ACD11 and in human ceramide-1-phosphate transfer protein (CPTP) is surrounded by cationic residues. Here, we investigated the functional regulation of ACD11 and CPTP by anionic phosphoglycerides and found that 1 palmitoyl-2-oleoyl-phosphatidic acid or 1-palmitoyl-2-oleoyl-phosphatidylglycerol (≈ 15 mol%) in C1P-source vesicles depressed C1P intermembrane transfer...
December 23, 2016: Journal of Biological Chemistry
Taylor E Miller, Julian Gomez-Cambronero
The removal of mRNA transcripts poly(A) tails by 3-5 exonucleases is the rate-limiting step in mRNA decay in eukaryotes. Known cellular deadenylases are, the CCR4-NOT and PAN complexes, and poly(A)-specific ribonuclease (PARN). The physiological roles and regulation for PARN is beginning to be elucidated. Since phospholipase D (PLD2 isoform) gene expression is upregulated in breast cancer cells and PARN is downregulated, we examined whether a signaling connection existed between these two enzymes. Silencing PARN with siRNA led to an increase in PLD2 protein and overexpression of PARN did the opposite...
December 23, 2016: Biology Open
Jingxin Shao, Caixia Wen, Mingjun Xuan, Hongyue Zhang, Johannes Frueh, Mingwei Wan, Lianghui Gao, Qiang He
Lipid bilayer membranes supported on polyelectrolyte multilayers are widely used as a new biomembrane model that connects biological and artificial materials since these ultrathin polyelectrolyte supports may mimic the role of the extracellular matrix and cell skeleton in living systems. Polyelectrolyte multilayers were fabricated by a layer-by-layer self-assembly technique. A quartz crystal microbalance with dissipation was used in real time to monitor the interaction between phospholipids and polyelectrolytes in situ on a planar substrate...
January 18, 2017: Physical Chemistry Chemical Physics: PCCP
Petter Holland, Helene Knævelsrud, Kristiane Søreng, Benan J Mathai, Alf Håkon Lystad, Serhiy Pankiv, Gunnveig T Bjørndal, Sebastian W Schultz, Viola H Lobert, Robin B Chan, Bowen Zhou, Knut Liestøl, Sven R Carlsson, Thomas J Melia, Gilbert Di Paolo, Anne Simonsen
A fundamental question is how autophagosome formation is regulated. Here we show that the PX domain protein HS1BP3 is a negative regulator of autophagosome formation. HS1BP3 depletion increased the formation of LC3-positive autophagosomes and degradation of cargo both in human cell culture and in zebrafish. HS1BP3 is localized to ATG16L1- and ATG9-positive autophagosome precursors and we show that HS1BP3 binds phosphatidic acid (PA) through its PX domain. Furthermore, we find the total PA content of cells to be significantly upregulated in the absence of HS1BP3, as a result of increased activity of the PA-producing enzyme phospholipase D (PLD) and increased localization of PLD1 to ATG16L1-positive membranes...
December 22, 2016: Nature Communications
Elena Andrada, María Almena, Julia Sáez de Guinoa, Sara V Merino-Cortes, Rosa Liébana, Raquel Arcos, Silvia Carrasco, Yolanda R Carrasco, Isabel Merida
The antigen-induced formation of an immune synapse (IS) between T cells and antigen-presenting cells results in the rapid generation of the lipid second messenger diacylglycerol (DAG) in T cells. Diacylglycerol kinase ζ (DGKζ) converts DAG into phosphatidic acid (PA). Cytotoxic T lymphocytes (CTLs) from mice deficient in DGKζ have enhanced antiviral and antitumor activities, indicating that the amount of DAG controls the effectiveness of the T cell response. We characterized the second C1 domain of protein kinase Cθ (PKCθ), a DAG-binding protein that is specifically recruited to the IS, as a biological sensor to observe the generation of a DAG gradient during IS formation...
December 20, 2016: Science Signaling
Salome Boroda, Maria Niccum, Vidisha Raje, Benjamin W Purow, Thurl E Harris
Diacylglycerol kinase alpha (DGKα) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Recently, DGKα was identified as a therapeutic target in various cancers, as well as in immunotherapy. Application of small-molecule DGK inhibitors, R59022 and R59949, induces cancer cell death in vitro and in vivo. The pharmacokinetics of these compounds in mice, however, are poor. Thus, there is a need to discover additional DGK inhibitors not only to validate these enzymes as targets in oncology, but also to achieve a better understanding of their biology...
October 27, 2016: Biochemical Pharmacology
Qing-Yu Zhang, Li-Xin Niu, Rui Yu, Xiao-Xiao Zhang, Zhang-Zhen Bai, Ke Duan, Qing-Hua Gao, Yan-Long Zhang
Tree peony (Paeonia section Moutan DC.) is an excellent woody oil crop, and the cloning and functional analysis of genes related to fatty acid (FA) metabolism from this organism has not been reported. Lysophosphatidic acid acyltransferase (LPAAT), which converts lysophosphatidic acid (LPA) to phosphatidic acid (PA), catalyzes the addition of fatty acyl moieties to the sn-2 position of the LPA glycerol backbone in triacylglycerol (TAG) biosynthesis. This project reports a putative lysophosphatidic acid acyltransferase gene PrLPAAT1 isolated from Paeonia rockii...
December 16, 2016: Applied Biochemistry and Biotechnology
Damien Jacot, Nicolò Tosetti, Isa Pires, Jessica Stock, Arnault Graindorge, Yu-Fu Hung, Huijong Han, Rita Tewari, Inari Kursula, Dominique Soldati-Favre
Apicomplexa exhibit a unique form of substrate-dependent gliding motility central for host cell invasion and parasite dissemination. Gliding is powered by rearward translocation of apically secreted transmembrane adhesins via their interaction with the parasite actomyosin system. We report a conserved armadillo and pleckstrin homology (PH) domain-containing protein, termed glideosome-associated connector (GAC), that mediates apicomplexan gliding motility, invasion, and egress by connecting the micronemal adhesins with the actomyosin system...
December 14, 2016: Cell Host & Microbe
Jang Ho Hur, Shi-Young Park, Claudia Dall'Armi, Jae Sung Lee, Gilbert Di Paolo, Hui-Young Lee, Mee-Sup Yoon, Do Sik Min, Cheol Soo Choi
Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides (TG) as lipid droplets in the liver. Although lipid-metabolizing enzymes are considered important in NAFLD, the involvement of phospholipase D1 (PLD1) has not yet been studied. Here, we show that the genetic ablation of PLD1 in mice induces NAFLD due to an autophagy defect. PLD1 expression was decreased in high-fat diet-induced NAFLD. Subsequently, PLD1 deficiency led to an increase in hepatic TGs and liver weight...
December 15, 2016: Scientific Reports
E Nicholas Petersen, Hae-Won Chung, Arman Nayebosadri, Scott B Hansen
The sensing of physical force, mechanosensation, underlies two of five human senses-touch and hearing. How transduction of force in a membrane occurs remains unclear. We asked if a biological membrane could employ kinetic energy to transduce a signal absent tension. Here we show that lipid rafts are dynamic compartments that inactivate the signalling enzyme phospholipase D2 (PLD2) by sequestering the enzyme from its substrate. Mechanical disruption of the lipid rafts activates PLD2 by mixing the enzyme with its substrate to produce the signalling lipid phosphatidic acid (PA)...
December 15, 2016: Nature Communications
Salome Boroda, Maria Niccum, Vidisha Raje, Benjamin W Purow, Thurl E Harris
Diacylglycerol kinase alpha (DGKα) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Recently, DGKα was identified as a therapeutic target in various cancers, as well as in immunotherapy. Application of small-molecule DGK inhibitors, R59022 and R59949, induces cancer cell death in vitro and in vivo. The pharmacokinetics of these compounds in mice, however, are poor. Thus, there is a need to discover additional DGK inhibitors not only to validate these enzymes as targets in oncology, but also to achieve a better understanding of their biology...
January 1, 2017: Biochemical Pharmacology
Gianluca Baldanzi, Valentina Bettio, Valeria Malacarne, Andrea Graziani
Diacylglycerol kinases (DGKs) terminate diacylglycerol (DAG) signaling and promote phosphatidic acid (PA) production. Isoform specific regulation of DGKs activity and localization allows DGKs to shape the DAG and PA gradients. The capacity of DGKs to constrain the areas of DAG signaling is exemplified by their role in defining the contact interface between T cells and antigen presenting cells: the immune synapse. Upon T cell receptor engagement, both DGK α and ζ metabolize DAG at the immune synapse thus constraining DAG signaling...
2016: Frontiers in Cell and Developmental Biology
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