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PI(4,5)P2

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https://www.readbyqxmd.com/read/28209843/lipid-transport-by-tmem24-at-er-plasma-membrane-contacts-regulates-pulsatile-insulin-secretion
#1
Joshua A Lees, Mirko Messa, Elizabeth Wen Sun, Heather Wheeler, Federico Torta, Markus R Wenk, Pietro De Camilli, Karin M Reinisch
Insulin is released by β cells in pulses regulated by calcium and phosphoinositide signaling. Here, we describe how transmembrane protein 24 (TMEM24) helps coordinate these signaling events. We showed that TMEM24 is an endoplasmic reticulum (ER)-anchored membrane protein whose reversible localization to ER-plasma membrane (PM) contacts is governed by phosphorylation and dephosphorylation in response to oscillations in cytosolic calcium. A lipid-binding module in TMEM24 transports the phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] precursor phosphatidylinositol between bilayers, allowing replenishment of PI(4,5)P2 hydrolyzed during signaling...
February 17, 2017: Science
https://www.readbyqxmd.com/read/28196852/inpp4b-and-pten-loss-leads-to-pi-3-4-p2-accumulation-and-inhibition-of-pi3k-in-tnbc
#2
Darien E Reed, Kevan M Shokat
: Triple-negative breast cancer [TNBC, lacks expression of estrogen receptor (ER), progesterone receptor (PR) and amplification of HER2/Neu] remains one of the most aggressive subtypes, affects the youngest patients and still lacks an effective targeted therapy(1,2). Both phosphatidylinositol-3-kinase (PI3K)-α and -β contribute to oncogenesis of solid tumors, including the development of breast cancer(3). Inositol polyphosphate-4-phosphatase type II (INPP4B) catalyzes the removal of the 4'-phosphate of phosphatidylinositol-(3,4-bisphosphate (PI-3,4-P2) creating phosphatidylinositol-3-phosphate(4)...
February 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28177616/calcium-directly-regulates-phosphatidylinositol-4-5-bisphosphate-headgroup-conformation-and-recognition
#3
Eva Bilkova, Roman Pleskot, Sami Rissanen, Simou Sun, Aleksander Czogalla, Lukasz Cwiklik, Tomasz Rog, Ilpo Vattulainen, Paul S Cremer, Pavel Jungwirth, Ünal Coskun
The orchestrated recognition of phosphoinositides and concomitant intracellular release of Ca2+ is pivotal to almost every aspect of cellular processes, including membrane homeostasis, cell division and growth, vesicle trafficking, as well as secretion. Although Ca2+ is known to directly impact phosphoinositide clustering, little is known about the molecular basis for this or its significance in cellular signaling. Here, we study the direct interaction of Ca2+ with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), the main lipid marker of the plasma membrane...
February 8, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28167678/ypk1-ypk2-kinases-maintain-rho1-at-the-plasma-membrane-by-flippase-dependent-lipid-remodelling-after-membrane-stresses
#4
Riko Hatakeyama, Keiko Kono, Satoshi Yoshida
The plasma membrane (PM) is frequently challenged by mechanical stresses. In budding yeast, TORC2-Ypk1/Ypk2 kinase cascade plays a critical role in PM stress responses by reorganizing the actin cytoskeleton via Rho1 GTPase. However, the molecular mechanism by which TORC2-Ypk1/Ypk2 regulates Rho1 is not well defined. Here, we found that Ypk1/Ypk2 maintain PM localization of Rho1 under PM stress via spatial reorganization of the lipids including phosphatidylserine (PS). Genetic evidence suggests that this process is mediated by the Lem3-containing lipid flippase...
February 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28157504/pi-3-4-5-p3-engagement-restricts-akt-activity-to-cellular-membranes
#5
Michael Ebner, Iva Lučić, Thomas A Leonard, Ivan Yudushkin
Protein kinase B/Akt regulates cellular metabolism, survival, and proliferation in response to hormones and growth factors. Hyperactivation of Akt is frequently observed in cancer, while Akt inactivation is associated with severe diabetes. Here, we investigated the molecular and cellular mechanisms that maintain Akt activity proportional to the activating stimulus. We show that binding of phosphatidylinositol-3,4,5-trisphosphate (PIP3) or PI(3,4)P2 to the PH domain allosterically activates Akt by promoting high-affinity substrate binding...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28157263/a-phosphoinositide-specific-phospholipase-c-pathway-elicits-stress-induced-ca-2-signals-and-confers-salt-tolerance-to-rice
#6
Li Li, Fawei Wang, Peiwen Yan, Wen Jing, Chunxia Zhang, Jörg Kudla, Wenhua Zhang
In animal cells, phospholipase C (PLC) isoforms predominantly hydrolyze phosphatidylinositol-4,5-biphosphates [PtdIns(4,5)P2 ] into the second messengers diacylglycerol (DAG) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3 ] to regulate diverse biological processes. By contrast, the molecular mechanisms and physiological significance of PLC signaling in plants still awaits full elucidation. Here, we identified a rice (Oryza sativa cv) PI-PLC, OsPLC1, which preferred to hydrolyze phosphatidylinositol-4-phosphate (PtdIns4P) and elicited stress-induced Ca(2+) signals regulating salt tolerance...
February 3, 2017: New Phytologist
https://www.readbyqxmd.com/read/28154160/tubby-family-proteins-are-adapters-for-ciliary-trafficking-of-integral-membrane-proteins
#7
Hemant B Badgandi, Sun-Hee Hwang, Issei S Shimada, Evan Loriot, Saikat Mukhopadhyay
The primary cilium is a paradigmatic organelle for studying compartmentalized signaling; however, unlike soluble protein trafficking, processes targeting integral membrane proteins to cilia are poorly understood. In this study, we determine that the tubby family protein TULP3 functions as a general adapter for ciliary trafficking of structurally diverse integral membrane cargo, including multiple reported and novel rhodopsin family G protein-coupled receptors (GPCRs) and the polycystic kidney disease-causing polycystin 1/2 complex...
February 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28143933/filopodia-formation-and-endosome-clustering-induced-by-mutant-plus-end-directed-myosin-vi
#8
Thomas A Masters, Folma Buss
Myosin VI (MYO6) is the only myosin known to move toward the minus end of actin filaments. It has roles in numerous cellular processes, including maintenance of stereocilia structure, endocytosis, and autophagosome maturation. However, the functional necessity of minus-end-directed movement along actin is unclear as the underlying architecture of the local actin network is often unknown. To address this question, we engineered a mutant of MYO6, MYO6+, which undergoes plus-end-directed movement while retaining physiological cargo interactions in the tail...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28138522/the-activation-loop-of-pip5k-functions-as-a-membrane-sensor-essential-for-lipid-substrate-processing
#9
Aizhuo Liu, Dexin Sui, Dianqing Wu, Jian Hu
Phosphatidylinositol 4-phosphate 5-kinase (PIP5K), a representative member of the phosphatidylinositol phosphate kinase (PIPK) family, is a major enzyme that biosynthesizes the signaling molecule PI(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) in eukaryotic cells. The stringent specificity toward lipid substrates and the high sensitivity to the membrane environment strongly suggest a membrane-sensing mechanism, but the underlying structural basis is still largely unknown. We present a nuclear magnetic resonance (NMR) study on a peptide commensurate with a PIP5K's activation loop, which has been reported to be a determinant of lipid substrate specificity and subcellular localization of PIP5K...
November 2016: Science Advances
https://www.readbyqxmd.com/read/28130450/rab8a-recruited-pi3k%C3%AE-regulates-signaling-and-cytokine-outputs-from-endosomal-toll-like-receptors
#10
Adam A Wall, Lin Luo, Yu Hung, Samuel J Tong, Nicholas D Condon, Antje Blumenthal, Matthew J Sweet, Jennifer L Stow
Lipopolysaccharide (LPS)-mediated activation of Toll-like receptor 4 (TLR4) in macrophages results in the coordinated release of proinflammatory cytokines, followed by regulatory mediators, to ensure that this potentially destructive pathway is tightly regulated. We previously showed that Rab8a recruits PI3Kγ for Akt-dependent signaling during TLR4 activation to limit the production of the pro-inflammatory cytokines IL-6 and IL-12p40, while enhancing the release of the regulatory/anti-inflammatory cytokine IL-10...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28106075/phosphatidylinositol-3-4-bisphosphate-regulates-neurite-initiation-and-dendrite-morphogenesis-via-actin-aggregation
#11
Shu-Xin Zhang, Li-Hui Duan, Shun-Ji He, Gui-Feng Zhuang, Xiang Yu
Neurite initiation is critical for neuronal morphogenesis and early neural circuit development. Recent studies showed that local actin aggregation underneath the cell membrane determined the site of neurite initiation. An immediately arising question is what signaling mechanism initiated actin aggregation. Here we demonstrate that local clustering of phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2), a phospholipid with relatively few known signaling functions, is necessary and sufficient for aggregating actin and promoting neuritogenesis...
January 20, 2017: Cell Research
https://www.readbyqxmd.com/read/28105255/pi3k-ship2-pten-pathway-in-cell-polarity-and-hepatitis-c-virus-pathogenesis
#12
REVIEW
Aline Awad, Ama Gassama-Diagne
Hepatitis C virus (HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides (PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases...
January 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28101851/importance-of-radioactive-labelling-to-elucidate-inositol-polyphosphate-signalling
#13
REVIEW
Miranda S C Wilson, Adolfo Saiardi
Inositol polyphosphates, in their water-soluble or lipid-bound forms, represent a large and multifaceted family of signalling molecules. Some inositol polyphosphates are well recognised as defining important signal transduction pathways, as in the case of the calcium release factor Ins(1,4,5)P3, generated by receptor activation-induced hydrolysis of the lipid PtdIns(4,5)P2 by phospholipase C. The birth of inositol polyphosphate research would not have occurred without the use of radioactive phosphate tracers that enabled the discovery of the "PI response"...
February 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28063499/analysis-of-phosphatidic-acid-binding-and-regulation-of-pipki-in-vitro-and-in-intact-cells
#14
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
#15
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
#16
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...
March 2017: Phytochemistry
https://www.readbyqxmd.com/read/28008947/self-assembly-of-hiv-1-gag-protein-on-lipid-membranes-generates-pi-4-5-p2-cholesterol-nanoclusters
#17
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
#18
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
#19
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
#20
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
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