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PI(4,5)P2

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https://www.readbyqxmd.com/read/28063499/analysis-of-phosphatidic-acid-binding-and-regulation-of-pipki-in-vitro-and-in-intact-cells
#1
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
https://www.readbyqxmd.com/read/28035047/the-acyltransferase-lycat-controls-specific-phosphoinositides-and-related-membrane-traffic
#2
Leslie N Bone, Roya M Dayam, Minhyoung Lee, Nozomu Kono, Gregory D Fairn, Hiroyuki Arai, Roberto J Botelho, Costin N Antonescu
Phosphoinositides (PIPs) are key regulators of membrane traffic and signaling. The interconversion of PIPs by lipid kinases and phosphatases regulates their functionality. Phosphatidylinositol (PI) and PIPs have a unique enrichment of 1-stearoyl-2-arachidonyl acyl species; however, the regulation and function of this specific acyl profile remains poorly understood. We examined the role of the PI acyltransferase LYCAT in control of PIPs and PIP-dependent membrane traffic. LYCAT silencing selectively perturbed the levels and localization of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] and phosphatidylinositol-3-phosphate and the membrane traffic dependent on these specific PIPs but was without effect on phosphatidylinositol-4-phosphate or biosynthetic membrane traffic...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28017365/acclimation-to-salt-modifies-the-activation-of-several-osmotic-stress-activated-lipid-signalling-pathways-in-chlamydomonas
#3
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
https://www.readbyqxmd.com/read/28008947/self-assembly-of-hiv-1-gag-protein-on-lipid-membranes-generates-pi-4-5-p2-cholesterol-nanoclusters
#4
Naresh Yandrapalli, Quentin Lubart, Hanumant S Tanwar, Catherine Picart, Johnson Mak, Delphine Muriaux, Cyril Favard
The self-assembly of HIV-1 Gag polyprotein at the inner leaflet of the cell host plasma membrane is the key orchestrator of virus assembly. The binding between Gag and the plasma membrane is mediated by specific interaction of the Gag matrix domain and the PI(4,5)P2 lipid (PIP2). It is unknown whether this interaction could lead to local reorganization of the plasma membrane lipids. In this study, using model membranes, we examined the ability of Gag to segregate specific lipids upon self-assembly. We show for the first time that Gag self-assembly is responsible for the formation of PIP2 lipid nanoclusters, enriched in cholesterol but not in sphingomyelin...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27998989/inpp5e-regulates-phosphoinositide-dependent-cilia-transition-zone-function
#5
Jennifer M Dyson, Sarah E Conduit, Sandra J Feeney, Sandra Hakim, Tia DiTommaso, Alex J Fulcher, Absorn Sriratana, Georg Ramm, Kristy A Horan, Rajendra Gurung, Carol Wicking, Ian Smyth, Christina A Mitchell
Human ciliopathies, including Joubert syndrome (JBTS), arise from cilia dysfunction. The inositol polyphosphate 5-phosphatase INPP5E localizes to cilia and is mutated in JBTS. Murine Inpp5e ablation is embryonically lethal and recapitulates JBTS, including neural tube defects and polydactyly; however, the underlying defects in cilia signaling and the function of INPP5E at cilia are still emerging. We report Inpp5e(-/-) embryos exhibit aberrant Hedgehog-dependent patterning with reduced Hedgehog signaling. Using mouse genetics, we show increasing Hedgehog signaling via Smoothened M2 expression rescues some Inpp5e(-/-) ciliopathy phenotypes and "normalizes" Hedgehog signaling...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/27984142/broad-substrate-affinity-and-catalytic-diversity-of-fibrinolytic-enzyme-from-pheretima-posthumous-purification-and-molecular-characterization-study
#6
Mahendra Kumar Verma, K K Pulicherla
In this research, a serine protease was isolated and purified from Indian earthworm Pheretima posthumous by fractionation with ammonium sulfate followed by ion exchange and size exclusion chromatography. The molecular weight of purified protease was determined 29.5kDa by Maldi-TOF/MS. The enzyme exhibited a maximum proteolytic activity of 1.2U/ml with specific activity of 17.65U/mg at pH 8 and temperature 40°C. 2D electrophoresis study illustrated purity of enzyme, purified as a single peptide and isoelectric point (pI) 4...
February 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27932583/inhibition-of-hiv-1-gag-membrane-interactions-by-specific-rnas
#7
Gabrielle C Todd, Alice A Duchon, Jingga Inlora, Erik D Olson, Karin Musier-Forsyth, Akira Ono
HIV-1 particle assembly, which occurs at the plasma membrane (PM) of cells, is driven by the viral polyprotein, Gag. Gag recognizes phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2], a PM-specific phospholipid, via the highly basic region (HBR) in its N-terminal matrix (MA) domain. The HBR is also known to bind to RNA. We have previously shown using an in vitro liposome binding assay that RNA inhibits Gag binding to membranes that lack PI(4,5)P2. If this RNA block is removed by RNase treatment, Gag can bind non-specifically to other negatively charged membranes...
December 8, 2016: RNA
https://www.readbyqxmd.com/read/27925395/persistency-of-enlarged-autolysosomes-underscores-nanoparticle-induced-autophagy-in-hepatocytes
#8
Ji-Qian Zhang, Wei Zhou, Sha-Sha Zhu, Jun Lin, Peng-Fei Wei, Fen-Fen Li, Pei-Pei Jin, Han Yao, Yun-Jiao Zhang, Yi Hu, Yi-Ming Liu, Ming Chen, Zheng-Quan Li, Xue-Sheng Liu, Li Bai, Long-Ping Wen
The diverse biological effects of nanomaterials form the basis for their applications in biomedicine but also cause safety issues. Induction of autophagy is a cellular response after nanoparticles exposure. It may be beneficial in some circumstances, yet autophagy-mediated toxicity raises an alarming concern. Previously, it has been reported that upconversion nanoparticles (UCNs) elicit liver damage, with autophagy contributing most of this toxicity. However, the detailed mechanism is unclear. This study reveals persistent presence of enlarged autolysosomes in hepatocytes after exposure to UCNs and SiO2 nanoparticles both in vitro and in vivo...
December 7, 2016: Small
https://www.readbyqxmd.com/read/27910774/comparison-of-the-chemical-composition-and-bioactive-components-of-fruiting-bodies-and-submerged-cultured-mycelia-of-the-willow-bracket-medicinal-mushroom-phellinus-igniarius-agaricomycetes
#9
Huawei Zeng, Wenfeng Wang, Menghua Ma, Guohua Xu, Mei Ying-Jie, Jianfan Sund
Chemical compositions and bioactive ingredients of dried fruiting bodies from Phellinus igniarius (CGMCC no. 50095) (P1) and submerged culture of Ph. igniarius dried mycelia (P2) were investigated in this study. It was found that glutamic acid was regarded as a major amino acid in P1 (1.20%) and was approximately 2.55-fold higher than that in P2 (0.47%). Total amino acids in P1 (5.36%) were slightly higher than in P2 (4.09%). The amounts of iron, zinc, copper, and manganese in P1 were 1.96-3.42 times as high as those in P2, whereas potassium, sodium, and magnesium in P2 were almost 2...
2016: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/27888240/topological-organisation-of-the-phosphatidylinositol-4-5-bisphosphate-phospholipase-c-resynthesis-cycle-pitps-bridge-the-er-pm-gap
#10
REVIEW
Shamshad Cockcroft, Padinjat Raghu
Phospholipase C (PLC) is a receptor-regulated enzyme that hydrolyses phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) at the plasma membrane (PM) triggering three biochemical consequences, the generation of soluble inositol 1,4,5-trisphosphate (IP3), membrane-associated diacylglycerol (DG) and the consumption of PM PI(4,5)P2 Each of these three signals triggers multiple molecular processes impacting key cellular properties. The activation of PLC also triggers a sequence of biochemical reactions, collectively referred to as the PI(4,5)P2 cycle that culminates in the resynthesis of this lipid...
December 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27881774/interactions-between-snap-25-and-synaptotagmin-1-are-involved-in-vesicle-priming-clamping-spontaneous-and-stimulating-evoked-neurotransmission
#11
Melanie Schupp, Jörg Malsam, Marvin Ruiter, Andrea Scheutzow, Keimpe D B Wierda, Thomas H Söllner, Jakob B Sørensen
: Whether interactions between synaptotagmin-1 (syt-1) and the soluble NSF attachment protein receptors (SNAREs) are required during neurotransmission is debated. We examined five SNAP-25 mutations designed to interfere with syt-1 interactions. One mutation, D51/E52/E55A, targeted negative charges within region II of the primary interface (Zhou et al., 2015); two mutations targeted region I (D166A and D166/E170A) and one mutation targeted both (D51/E52/E55/D166A). The final mutation (D186/D193A) targeted C-terminal residues not expected to interact with syt-1...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27870828/agonist-stimulated-phosphatidylinositol-3-4-5-trisphosphate-generation-by-scaffolded-phosphoinositide-kinases
#12
Suyong Choi, Andrew C Hedman, Samar Sayedyahossein, Narendra Thapa, David B Sacks, Richard A Anderson
Generation of the lipid messenger phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) is crucial for development, cell growth and survival, and motility, and it becomes dysfunctional in many diseases including cancers. Here we reveal a mechanism for PtdIns(3,4,5)P3 generation by scaffolded phosphoinositide kinases. In this pathway, class I phosphatidylinositol-3-OH kinase (PI(3)K) is assembled by IQGAP1 with PI(4)KIIIα and PIPKIα, which sequentially generate PtdIns(3,4,5)P3 from phosphatidylinositol...
November 21, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27819060/the-hidden-conundrum-of-phosphoinositide-signaling-in-cancer
#13
Narendra Thapa, Xiaojun Tan, Suyong Choi, Paul F Lambert, Alan C Rapraeger, Richard A Anderson
Phosphoinositide 3-kinase (PI3K) generation of PI(3,4,5)P3 from PI(4,5)P2 and the subsequent activation of Akt and its downstream signaling cascades (e.g. mTORC1) dominates the landscape of phosphoinositide signaling axis in cancer research. However, PI(4,5)P2 is breaking its boundary as merely a substrate for PI3K and phospholipase C (PLC), and is now an established lipid messenger pivotal for different cellular events in cancer. Here, we review the phosphoinositide signaling axis in cancer, giving due weight to PI(4,5)P2 and its generating enzymes, the phosphatidylinositol phosphate (PIP) kinases (PIPKs)...
July 2016: Trends in Cancer
https://www.readbyqxmd.com/read/27805608/single-molecule-super-resolution-imaging-of-phosphatidylinositol-4-5-bisphosphate-in-the-plasma-membrane-with-novel-fluorescent-probes
#14
Chen Ji, Xuelin Lou
Phosphoinositides in the cell membrane are signaling lipids with multiple cellular functions. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a determinant phosphoinositide of the plasma membrane (PM), and it is required to modulate ion channels, actin dynamics, exocytosis, endocytosis, intracellular signaling, and many other cellular processes. However, the spatial organization of PI(4,5)P2 in the PM is controversial, and its nanoscale distribution is poorly understood due to the technical limitations of research approaches...
October 15, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27790796/functional-characterization-and-rescue-of-a-deep-intronic-mutation-in-ocrl-gene-responsible-for-lowe-syndrome
#15
John Rendu, Rodrick Montjean, Charles Coutton, Mohnish Suri, Gaetan Chicanne, Anne Petiot, Julie Brocard, Didier Grunwald, France Pietri Rouxel, Bernard Payrastre, Joel Lunardi, Olivier Dorseuil, Isabelle Marty, Julien Fauré
Dent-2 disease and Lowe syndrome are two pathologies caused by mutations in inositol polyphosphate 5-phosphatase OCRL gene. Both conditions share proximal tubulopathy evolving to chronic kidney failure. Lowe syndrome is in addition defined by a bilateral congenital cataract, intellectual disability, and hypotonia. The pathology evolves in two decades to a severe condition with renal complications and a fatal issue. We describe here a proof of principle for a targeted gene therapy on a mutation of the OCRL gene that is associated with Lowe syndrome...
February 2017: Human Mutation
https://www.readbyqxmd.com/read/27757455/the-ebola-virus-protein-vp40-hexamer-enhances-the-clustering-of-pi-4-5-p2-lipids-in-the-plasma-membrane
#16
Jeevan B Gc, Bernard S Gerstman, Robert V Stahelin, Prem P Chapagain
The Ebola virus is a lipid-enveloped virus that obtains its lipid coat from the plasma membrane of the host cell it infects during the budding process. The Ebola virus protein VP40 localizes to the inner leaflet of the plasma membrane and forms the viral matrix, which provides the major structure for the Ebola virus particles. VP40 is initially a dimer that rearranges to a hexameric structure that mediates budding. VP40 hexamers and larger filaments have been shown to be stabilized by PI(4,5)P2 in the plasma membrane inner leaflet...
October 19, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27725450/effects-of-glycerophospholipids-on-ceramide-kinase-activity-cardiolipin-affected-cellular-formation-of-ceramide-1-phosphate
#17
Wataru Matsuzaki, Hiromasa Takahashi, Hiroyuki Nakamura, Toshihiko Murayama
Ceramide kinase (CerK) and ceramide-1-phosphate (C1P) are involved in various cellular functions, while regulation of the enzyme activity has not been well elucidated. We herein investigated the effects of several glycerophospholipids on human recombinant CerK activity with CaCl2 and MgCl2 by measuring the formation of fluorescent labeled C1P in vitro. CerK activities were 44.1±11.4 (pmol/µg/min) with vehicle, 137±29 with 2 mM CaCl2, and 144±32 with 2 mM MgCl2 in the glycerol/albumin buffer. The addition of glycerophospholipids such as phosphatidylcholine, phosphatidylinositol (PI), PI 4,5-bisphosphate (PI(4,5)P2), and phosphatidic acid had no effect on CerK activity with CaCl2, although PI(4,5)P2 and phosphatidic acid bound to CerK in the lipid-protein overlay assay...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27716613/lipid-phosphatase-ship2-functions-as-oncogene-in-colorectal-cancer-by-regulating-pkb-activation
#18
Elmer Hoekstra, Asha M Das, Marcella Willemsen, Marloes Swets, Peter J K Kuppen, Christien J van der Woude, Marco J Bruno, Jigisha P Shah, Timo L M Ten Hagen, John D Chisholm, William G Kerr, Maikel P Peppelenbosch, Gwenny M Fuhler
Colorectal cancer (CRC) is the second most common cause of cancer-related death, encouraging the search for novel therapeutic targets affecting tumor cell proliferation and migration. These cellular processes are under tight control of two opposing groups of enzymes; kinases and phosphatases. Aberrant activity of kinases is observed in many forms of cancer and as phosphatases counteract such "oncogenic" kinases, it is generally assumed that phosphatases function as tumor suppressors. However, emerging evidence suggests that the lipid phosphatase SH2-domain-containing 5 inositol phosphatase (SHIP2), encoded by the INPPL1 gene, may act as an oncogene...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27706148/calcium-stimulates-self-assembly-of-protein-kinase-c-%C3%AE-in-vitro
#19
Carter J Swanson, Ruth F Sommese, Karl J Petersen, Michael Ritt, Joshua Karslake, David D Thomas, Sivaraj Sivaramakrishnan
Protein kinase C α (PKCα) is a nodal regulator in several intracellular signaling networks. PKCα is composed of modular domains that interact with each other to dynamically regulate spatial-temporal function. We find that PKCα specifically, rapidly and reversibly self-assembles in the presence of calcium in vitro. This phenomenon is dependent on, and can be modulated by an intramolecular interaction between the C1a and C2 protein domains of PKCα. Next, we monitor self-assembly of PKC-mCitrine fusion proteins using time-resolved and steady-state homoFRET...
2016: PloS One
https://www.readbyqxmd.com/read/27698019/ralf-mediated-activation-of-arf6-controls-rickettsia-typhi-invasion-by-co-opting-phosphoinositol-metabolism
#20
Kristen E Rennoll-Bankert, M Sayeedur Rahman, Mark L Guillotte, Stephanie S Lehman, Magda Beier-Sexton, Joseph J Gillespie, Abdu F Azad
Rickettsiae are obligate intracellular pathogens that induce their uptake into nonphagocytic cells; however, the events instigating this process are incompletely understood. Importantly, diverse Rickettsia species are predicted to utilize divergent mechanisms to colonize host cells, as nearly all adhesins and effectors involved in host cell entry are differentially encoded in diverse Rickettsia species. One particular effector, RalF, a Sec7 domain-containing protein that functions as a guanine nucleotide exchange factor of ADP-ribosylation factors (Arfs), is critical for Rickettsia typhi (typhus group rickettsiae) entry but pseudogenized or absent from spotted fever group rickettsiae...
December 2016: Infection and Immunity
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