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PI(4,5)P2

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https://www.readbyqxmd.com/read/28634262/rassf4-regulator-of-plasma-membrane-pi-4-5-p2
#1
Eamonn J Dickson
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a negatively charged phospholipid that plays a major role in recruiting and regulating proteins at the plasma membrane-cytosol interface. In this issue, Chen et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201606047) demonstrate that RAS association domain family 4 (RASSF4) positively influences PI(4,5)P2 synthesis through ARF6-dependent regulation of PIP5K.
June 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28621027/aromatic-amino-acids-and-their-relevance-in-the-specificity-of-the-ph-domain
#2
Ja Morales, M Sobol, L C Rodriguez-Zapata, P Hozak, E Castano
Phosphoinositides are phosphatidylinositol derived, well known to be second messengers in various cell signaling pathways as well as in processes such as cell differentiation, cellular stress response, gene transcription, and chromatin remodeling. The pleckstrin homology domain of phospholipase C-delta 1 is responsible for recognizing and binding to PI(4,5)P2 and for this reason has been widely used to study this phosphoinositide as a biosensor when it is conjugated to a fluorescent tag. In this work, we modified the primary structure of pleckstrin homology domain by site-specific mutagenesis to change the specificity for phosphoinositides...
June 16, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28600435/rassf4-controls-soce-and-er-pm-junctions-through-regulation-of-pi-4-5-p2
#3
Yu-Ju Chen, Chi-Lun Chang, Wan-Ru Lee, Jen Liou
RAS association domain family 4 (RASSF4) is involved in tumorigenesis and regulation of the Hippo pathway. In this study, we identify new functional roles of RASSF4. First, we discovered that RASSF4 regulates store-operated Ca(2+) entry (SOCE), a fundamental Ca(2+) signaling mechanism, by affecting the translocation of the endoplasmic reticulum (ER) Ca(2+) sensor stromal interaction molecule 1 (STIM1) to ER-plasma membrane (PM) junctions. It was further revealed that RASSF4 regulates the formation of ER-PM junctions and the ER-PM tethering function of extended synaptotagmins E-Syt2 and E-Syt3...
June 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28574338/synchronized-hiv-assembly-by-tunable-pip2-changes-reveals-pip2-requirement-for-stable-gag-anchoring
#4
Frauke Mücksch, Vibor Laketa, Barbara Müller, Carsten Schultz, Hans-Georg Kräusslich
HIV-1 assembles at the plasma membrane (PM) of infected cells. PM association of the main structural protein Gag depends on its myristoylated MA domain and PM PI(4,5)P2. Using a novel chemical biology tool that allows rapidly tunable manipulation of PI(4,5)P2 levels in living cells, we show that depletion of PI(4,5)P2 completely prevents Gag PM targeting and assembly site formation. Unexpectedly, PI(4,5)P2 depletion also caused loss of pre-assembled Gag lattices from the PM. Subsequent restoration of PM PI(4,5)P2 reinduced assembly site formation even in the absence of new protein synthesis, indicating that the dissociated Gag molecules remained assembly competent...
June 2, 2017: ELife
https://www.readbyqxmd.com/read/28572395/mtorc1-activity-repression-by-late-endosomal-phosphatidylinositol-3-4-bisphosphate
#5
Andrea L Marat, Alexander Wallroth, Wen-Ting Lo, Rainer Müller, Giuseppe Danilo Norata, Marco Falasca, Carsten Schultz, Volker Haucke
Nutrient sensing by mechanistic target of rapamycin complex 1 (mTORC1) on lysosomes and late endosomes (LyLEs) regulates cell growth. Many factors stimulate mTORC1 activity, including the production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] by class I phosphatidylinositol 3-kinases (PI3Ks) at the plasma membrane. We investigated mechanisms that repress mTORC1 under conditions of growth factor deprivation. We identified phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2], synthesized by class II PI3K β (PI3KC2β) at LyLEs, as a negative regulator of mTORC1, whereas loss of PI3KC2β hyperactivated mTORC1...
June 2, 2017: Science
https://www.readbyqxmd.com/read/28569910/cations-induce-shape-remodeling-of-negatively-charged-phospholipid-membranes
#6
Z T Graber, Z Shi, T Baumgart
The divalent cation Ca(2+) is a key component in many cell signaling and membrane trafficking pathways. Ca(2+) signal transduction commonly occurs through interaction with protein partners. However, in this study we show a novel mechanism by which Ca(2+) may impact membrane structure. We find an asymmetric concentration of Ca(2+) across the membrane triggers deformation of membranes containing negatively charged lipids such as phosphatidylserine (PS) and phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). Membrane invaginations in vesicles were observed forming away from the leaflet with higher Ca(2+) concentration, showing that Ca(2+) induces negative curvature...
June 14, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28539432/golgi-associated-protein-kinase-c-%C3%AE%C2%B5-is-delivered-to-phagocytic-cups-role-of-phosphatidylinositol-4-phosphate
#7
Cheryl M Hanes, Anna E D'Amico, Takehiko Ueyama, Alexander C Wong, Xuexin Zhang, W Frederick Hynes, Margarida M Barroso, Nathaniel C Cady, Mohamed Trebak, Naoaki Saito, Michelle R Lennartz
Protein kinase C-ε (PKC-ε) at phagocytic cups mediates the membrane fusion necessary for efficient IgG-mediated phagocytosis. The C1B and pseudosubstrate (εPS) domains are necessary and sufficient for this concentration. C1B binds diacylglycerol; the docking partner for εPS is unknown. Liposome assays revealed that the εPS binds phosphatidylinositol 4-phosphate (PI4P) and PI(3,5)P2 Wortmannin, but not LY294002, inhibits PKC-ε concentration at cups and significantly reduces the rate of phagocytosis. As Wortmannin inhibits PI4 kinase, we hypothesized that PI4P mediates the PKC-ε concentration at cups and the rate of phagocytosis...
May 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28507506/differential-regulation-of-pi-4-5-p2-sensitivity-of-kv7-2-and-kv7-3-channels-by-calmodulin
#8
Carolina Gomis-Perez, Maria V Soldovieri, Covadonga Malo, Paolo Ambrosino, Maurizio Taglialatela, Pilar Areso, Alvaro Villarroel
HIGHLIGHTS - Calmodulin-dependent Kv7.2 current density without the need of binding calcium.- Kv7.2 current density increase is accompanied with resistance to PI(4,5)P2 depletion.- Kv7.3 current density is insensitive to calmodulin elevation.- Kv7.3 is more sensitive to PI(4,5)P2 depletion in the presence of calmodulin.- Apo-calmodulin influences PI(4,5)P2 dependence in a subunit specific manner. The identification and understanding of critical factors regulating M-current functional density, whose main components are Kv7...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28473699/ocular-pathology-of-oculocerebrorenal-syndrome-of-lowe-novel-mutations-and-genotype-phenotype-analysis
#9
Emilie Song, Na Luo, Jorge A Alvarado, Maria Lim, Cathleen Walnuss, Daniel Neely, Dan Spandau, Alireza Ghaffarieh, Yang Sun
Mutations in the OCRL1 gene result in the oculocerebrorenal syndrome of Lowe, with symptoms including congenital bilateral cataracts, glaucoma, renal failure, and neurological impairments. OCRL1 encodes an inositol polyphosphate 5-phosphatase which preferentially dephosphorylates phosphatidylinositide 4,5 bisphosphate (PI(4,5)P2). We have identified two novel mutations in two unrelated Lowe syndrome patients with congenital glaucoma. Novel deletion mutations are detected at c.739-742delAAAG in Lowe patient 1 and c...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28409542/inhibitory-receptor-fc%C3%AE-riib-mediates-the-effects-of-igg-on-a-phagosome-acidification-and-a-sequential-dephosphorylation-system-comprising-ships-and-inpp4a
#10
Tomohiro Segawa, Kaoru Hazeki, Kiyomi Nigorikawa, Atsuko Nukuda, Tomoki Tanizawa, Kenshiro Miyamoto, Shin Morioka, Osamu Hazeki
The relative abundance of phosphoinositide (PI) species on the phagosome membrane fluctuates over the course of phagocytosis. PtdIns(3,4,5)P3 and PtdIns(3,4)P2 rapidly increase in the forming of the phagocytic cup, following which they disappear after sealing of the cup. In the present study, we monitored the clearance of these PI species using the enhanced green fluorescent protein-fused pleckstrin homology domain of Akt, a fluorescence probe that binds both PtdIns(3,4,5)P3 and PtdIns(3,4)P2 in Raw 264.7 macrophages...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28377218/synergistic-activation-of-g-protein-gated-inwardly-rectifying-potassium-channels-by-cholesterol-and-pi-4-5-p2
#11
Anna N Bukiya, Avia Rosenhouse-Dantsker
G-protein gated inwardly rectifying potassium (GIRK or Kir3) channels play a major role in the control of the heart rate, and require the membrane phospholipid phosphatidylinositol-bis-phosphate (PI(4,5)P2) for activation. Recently, we have shown that the activity of the heterotetrameric Kir3.1/Kir3.4 channel that underlies atrial KACh currents was enhanced by cholesterol. Similarly, the activities of both the Kir3.4 homomer and its active pore mutant Kir3.4* (Kir3.4_S143T) were also enhanced by cholesterol...
July 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28358046/phosphatidylinositol-4-5-bisphosphate-dynamically-regulates-the-k2p-background-k-channel-task-2
#12
María Isabel Niemeyer, L Pablo Cid, Marc Paulais, Jacques Teulon, Francisco V Sepúlveda
Two-pore domain K2P K(+) channels responsible for the background K(+) conductance and the resting membrane potential, are also finely regulated by a variety of chemical, physical and physiological stimuli. Hormones and transmitters acting through Gq protein-coupled receptors (GqPCRs) modulate the activity of various K2P channels but the signalling involved has remained elusive, in particular whether dynamic regulation by membrane PI(4,5)P2, common among other classes of K(+) channels, affects K2P channels is controversial...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331029/the-sac1-domain-in-synaptojanin-is-required-for%C3%A2-autophagosome-maturation-at-presynaptic%C3%A2-terminals
#13
Roeland Vanhauwaert, Sabine Kuenen, Roy Masius, Adekunle Bademosi, Julia Manetsberger, Nils Schoovaerts, Laura Bounti, Serguei Gontcharenko, Jef Swerts, Sven Vilain, Marina Picillo, Paolo Barone, Shashini T Munshi, Femke Ms de Vrij, Steven A Kushner, Natalia V Gounko, Wim Mandemakers, Vincenzo Bonifati, Frederic A Meunier, Sandra-Fausia Soukup, Patrik Verstreken
Presynaptic terminals are metabolically active and accrue damage through continuous vesicle cycling. How synapses locally regulate protein homeostasis is poorly understood. We show that the presynaptic lipid phosphatase synaptojanin is required for macroautophagy, and this role is inhibited by the Parkinson's disease mutation R258Q. Synaptojanin drives synaptic endocytosis by dephosphorylating PI(4,5)P2, but this function appears normal in Synaptojanin(RQ) knock-in flies. Instead, R258Q affects the synaptojanin SAC1 domain that dephosphorylates PI(3)P and PI(3,5)P2, two lipids found in autophagosomal membranes...
May 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28292899/fission-yeast-myosin-i-facilitates-pi-4-5-p2-mediated-anchoring-of-cytoplasmic-dynein-to-the-cortex
#14
Jerrin Mathew Thankachan, Stephen Sukumar Nuthalapati, Nireekshit Addanki Tirumala, Vaishnavi Ananthanarayanan
Several key processes in the cell, such as vesicle transport and spindle positioning, are mediated by the motor protein cytoplasmic dynein, which produces force on the microtubule. For the functions that require movement of the centrosome and the associated nuclear material, dynein needs to have a stable attachment at the cell cortex. In fission yeast, Mcp5 is the anchor protein of dynein and is required for the oscillations of the horsetail nucleus during meiotic prophase. Although the role of Mcp5 in anchoring dynein to the cortex has been identified, it is unknown how Mcp5 associates with the membrane as well as the importance of the underlying attachment to the nuclear oscillations...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28276191/deleting-the-dag-kinase-dgk1-augments-yeast-vacuole-fusion-through-increased-ypt7-activity-and-altered-membrane-fluidity
#15
Gregory E Miner, Matthew L Starr, Logan R Hurst, Rutilio A Fratti
Diacylglycerol (DAG) is a fusogenic lipid that can be produced through phospholipase C activity on phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2 ], or through phosphatidic acid (PA) phosphatase activity. The fusion of Saccharomyces cerevisiae vacuoles requires DAG, PA and PI(4,5)P2 , and the production of these lipids is thought to provide temporally specific stoichiometries that are critical for each stage of fusion. Furthermore, DAG and PA can be interconverted by the DAG kinase Dgk1 and the PA phosphatase Pah1...
May 2017: Traffic
https://www.readbyqxmd.com/read/28247964/pi-3-4-p2-plays-critical-roles-in-the-regulation-of-focal-adhesion-dynamics-of-mda-mb-231-breast-cancer-cells
#16
Miki Fukumoto, Takeshi Ijuin, Tadaomi Takenawa
Phosphoinositides play pivotal roles in the regulation of cancer cell phenotypes. Among them, phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2 ) localizes to the invadopodia, and positively regulates tumor cell invasion. In this study, we examined the effect of PI(3,4)P2 on focal adhesion dynamics in MDA-MB-231 basal breast cancer cells. Knockdown of SHIP2, a phosphatidylinositol 3,4,5-trisphosphatase (PIP3 ) 5-phosphatase that generates PI(3,4)P2 , in MDA-MB-231 breast cancer cells, induced the development of focal adhesions and cell spreading, leading to the suppression of invasion...
May 2017: Cancer Science
https://www.readbyqxmd.com/read/28231468/parkinson-sac-domain-mutation-in-synaptojanin-1-impairs-clathrin-uncoating-at-synapses-and-triggers-dystrophic-changes-in-dopaminergic-axons
#17
Mian Cao, Yumei Wu, Ghazaleh Ashrafi, Amber J McCartney, Heather Wheeler, Eric A Bushong, Daniela Boassa, Mark H Ellisman, Timothy A Ryan, Pietro De Camilli
Synaptojanin 1 (SJ1) is a major presynaptic phosphatase that couples synaptic vesicle endocytosis to the dephosphorylation of PI(4,5)P2, a reaction needed for the shedding of endocytic factors from their membranes. While the role of SJ1's 5-phosphatase module in this process is well recognized, the contribution of its Sac phosphatase domain, whose preferred substrate is PI4P, remains unclear. Recently a homozygous mutation in its Sac domain was identified in early-onset parkinsonism patients. We show that mice carrying this mutation developed neurological manifestations similar to those of human patients...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28222177/phospholipid-binding-to-the-fak-catalytic-domain-impacts-function
#18
Jessica E Hall, Michael D Schaller
Focal adhesion kinase is an essential nonreceptor tyrosine kinase that plays an important role in development, in homeostasis and in the progression of human disease. Multiple stimuli activate FAK, which requires a change in structure from an autoinhibited to activated conformation. In the autoinhibited conformation the FERM domain associates with the catalytic domain of FAK and PI(4,5)P2 binding to the FERM domain plays a role in the release of autoinhibition, activating the enzyme. An in silico model of FAK/PI(4,5)P2 interaction suggests that residues on the catalytic domain interact with PI(4,5)P2, in addition to the known FERM domain PI(4,5)P2 binding site...
2017: PloS One
https://www.readbyqxmd.com/read/28209843/lipid-transport-by-tmem24-at-er-plasma-membrane-contacts-regulates-pulsatile-insulin-secretion
#19
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
#20
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. Both phosphatidylinositol-3-kinase (PI3K)-α and -β contribute to oncogenesis of solid tumors, including the development of breast cancer. 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...
June 2017: Molecular Cancer Research: MCR
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