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PI(4,5)P2

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
October 28, 2016: 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
#8
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
#9
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
#10
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
#11
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
#12
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 non-phagocytic 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 sec-7 domain containing protein that functions as a guanine nucleotide exchange factor of ADP-ribosylation factors (Arfs), is critical for R...
October 3, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27669036/skywalker-tbc1d24-has-a-lipid-binding-pocket-mutated-in-epilepsy-and-required-for-synaptic-function
#13
Baptiste Fischer, Kevin Lüthy, Jone Paesmans, Charlotte De Koninck, Ine Maes, Jef Swerts, Sabine Kuenen, Valerie Uytterhoeven, Patrik Verstreken, Wim Versées
Mutations in TBC1D24 cause severe epilepsy and DOORS syndrome, but the molecular mechanisms underlying these pathologies are unresolved. We solved the crystal structure of the TBC domain of the Drosophila ortholog Skywalker, revealing an unanticipated cationic pocket conserved among TBC1D24 homologs. Cocrystallization and biochemistry showed that this pocket binds phosphoinositides phosphorylated at the 4 and 5 positions. The most prevalent patient mutations affect the phosphoinositide-binding pocket and inhibit lipid binding...
September 26, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27650500/a-histidine-cluster-in-the-cytoplasmic-domain-of-the-na-h-exchanger-nhe1-confers-ph-sensitive-phospholipid-binding-and-regulates-transporter-activity
#14
Bradley A Webb, Katharine A White, Bree K Grillo-Hill, André Schönichen, Changhoon Choi, Diane L Barber
The Na-H exchanger NHE1 contributes to intracellular pH (pHi) homeostasis in normal cells and the constitutively increased pHi in cancer. NHE1 activity is allosterically regulated by intracellular protons, with greater activity at lower pHi However, the molecular mechanism for pH-dependent NHE1 activity remains incompletely resolved. We report that an evolutionarily conserved cluster of histidine residues located in the C-terminal cytoplasmic domain between two phosphatidylinositol 4,5-bisphosphate binding sites (PI(4,5)P2) of NHE1 confers pH-dependent PI(4,5)P2 binding and regulates NHE1 activity...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27641491/hiv-1-matrix-31-membrane-binding-peptide-interacts-differently-with-membranes-containing-ps-vs-pi-4-5-p2
#15
Lauren O'Neil, Kathryn Andenoro, Isabella Pagano, Laura Carroll, Leah Langer, Zachary Dell, Davina Perera, Bradley W Treece, Frank Heinrich, Mathias Lösche, John F Nagle, Stephanie Tristram-Nagle
Efficient assembly of HIV-1 at the plasma membrane (PM) of the T-cell specifically requires PI(4,5)P2. It was previously shown that a highly basic region (HBR) of the matrix protein (MA) on the Gag precursor polyprotein Pr55(Gag) is required for membrane association. MA is N-terminally myristoylated, which enhances its affinity to membranes. In this work we used X-ray scattering and neutron reflectivity to determine how the physical properties and structure of lipid bilayers respond to the addition of binding domain peptides, either in the myristoylated form (MA31myr) or without the myristoyl group (MA31)...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27601656/in-b-cells-phosphatidylinositol-5-phosphate-4-kinase-%C3%AE-synthesizes-pi-4-5-p2-to-impact-mtorc2-and-akt-signaling
#16
Simon J Bulley, Alaa Droubi, Jonathan H Clarke, Karen E Anderson, Len R Stephens, Phillip T Hawkins, Robin F Irvine
Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are enigmatic lipid kinases with physiological functions that are incompletely understood, not the least because genetic deletion and cell transfection have led to contradictory data. Here, we used the genetic tractability of DT40 cells to create cell lines in which endogenous PI5P4Kα was removed, either stably by genetic deletion or transiently (within 1 h) by tagging the endogenous protein genomically with the auxin degron. In both cases, removal impacted Akt phosphorylation, and by leaving one PI5P4Kα allele present but mutating it to be kinase-dead or have PI4P 5-kinase activity, we show that all of the effects on Akt phosphorylation were dependent on the ability of PI5P4Kα to synthesize phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] rather than to remove PI5P...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27589852/magnesium-dependent-ecto-atp-diphosphohydrolase-activity-in-leishmania-donovani
#17
Preeti Sinha, Ranjeet Kumar Paswan, Anjali Kumari, Sanjay Kumar, Sanjeeva Bimal, Pradeep Das, Chandra Shekhar Lal
In this work, we have described the expression of ecto-ATPDase on the external surface of Leishmania donovani. This enzyme has the ability to hydrolyze extracellular ATP. There is a low level of ATP hydrolysis in the absence of divalent cation 2.5 ± 0.51 nM Pi 10(7) cells/h which shows the divalent cation-dependent activity of this enzyme in the intact parasite. However, MgCl2 stimulated the ATP hydrolysis to a greater extent compared with CaCl2 and ZnCl2. This activity was also observed when replaced by MnCl2...
December 2016: Current Microbiology
https://www.readbyqxmd.com/read/27582103/both-clic4-and-clic5a-activate-erm-proteins-in-glomerular-endothelium
#18
Mahtab Tavasoli, Abass Al-Momany, Xin Wang, Laiji Li, John Clark Edwards, Barbara J Ballermann
The chloride intracellular channel (CLIC) 5A is expressed at very high levels in renal glomeruli, in both endothelial cells (EC) and podocytes. CLIC5A stimulates Rac1- and PI[4,5]P2-dependent ERM (ezrin, radixin, moesin) activation. ERM proteins, in turn, function in lumen formation and in the development of actin-based cellular projections. In mice lacking CLIC5A, ERM phosphorylation is profoundly reduced in podocytes, but preserved in glomerular EC. Since glomerular EC also express CLIC4, we reasoned if CLIC4 activates ERM proteins like CLIC5A, then CLIC4 could compensate for the CLIC5A loss in glomerular EC...
August 31, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27578150/molecular-aspects-of-the-interaction-between-mason-pfizer-monkey-virus-matrix-protein-and-artificial-phospholipid-membrane
#19
P Junková, J Prchal, V Spiwok, R Pleskot, J Kadlec, L Krásný, R Hynek, R Hrabal, T Ruml
The Mason-Pfizer monkey virus is a type D retrovirus, which assembles its immature particles in the cytoplasm prior to their transport to the host cell membrane. The association with the membrane is mediated by the N-terminally myristoylated matrix protein. To reveal the role of particular residues which are involved in the capsid-membrane interaction, covalent labelling of arginine, lysine and tyrosine residues of the Mason-Pfizer monkey virus matrix protein bound to artificial liposomes containing 95% of phosphatidylcholine and 5% phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2 ) was performed...
August 31, 2016: Proteins
https://www.readbyqxmd.com/read/27528604/the-vesicle-priming-factor-caps-functions-as-a-homodimer-via-c2-domain-interactions-to-promote-regulated-vesicle-exocytosis
#20
Matt Petrie, Joseph Esquibel, Greg Kabachinski, Stephanie Maciuba, Hirohide Takahashi, J Michael Edwardson, Thomas F J Martin
Neurotransmitters and peptide hormones are secreted by regulated vesicle exocytosis. CAPS (also known as CADPS) is a 145-kDa cytosolic and peripheral membrane protein required for vesicle docking and priming steps that precede Ca(2+)-triggered vesicle exocytosis. CAPS binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and SNARE proteins and is proposed to promote SNARE protein complex assembly for vesicle docking and priming. We characterized purified soluble CAPS as mainly monomer in equilibrium with small amounts of dimer...
September 30, 2016: Journal of Biological Chemistry
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