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PI(4,5)P2

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https://www.readbyqxmd.com/read/28932942/required-hydrophobicity-of-fluorescent-reporters-for-phosphatidylinositol-family-of-lipid-enzymes
#1
Jarod Waybright, Weigang Huang, Angela Proctor, Xiaoyang Wang, Nancy L Allbritton, Qisheng Zhang
The phosphatidylinositol (PtdIns) family of lipids plays important roles in cell differentiation, proliferation, and migration. Abnormal expression, mutation, or regulation of their metabolic enzymes has been associated with various human diseases such as cancer, diabetes, and bipolar disorder. Recently, fluorescent derivatives have increasingly been used as chemical probes to monitor either lipid localization or enzymatic activity. However, the requirements of a good probe have not been well defined, particularly modifications on the diacylglycerol side chain partly due to challenges in generating PtdIns lipids...
September 20, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28923975/control-of-actin-polymerization-via-the-coincidence-of-phosphoinositides-and-high-membrane-curvature
#2
Frederic Daste, Astrid Walrant, Mikkel R Holst, Jonathan R Gadsby, Julia Mason, Ji-Eun Lee, Daniel Brook, Marcel Mettlen, Elin Larsson, Steven F Lee, Richard Lundmark, Jennifer L Gallop
The conditional use of actin during clathrin-mediated endocytosis in mammalian cells suggests that the cell controls whether and how actin is used. Using a combination of biochemical reconstitution and mammalian cell culture, we elucidate a mechanism by which the coincidence of PI(4,5)P2 and PI(3)P in a curved vesicle triggers actin polymerization. At clathrin-coated pits, PI(3)P is produced by the INPP4A hydrolysis of PI(3,4)P2, and this is necessary for actin-driven endocytosis. Both Cdc42⋅guanosine triphosphate and SNX9 activate N-WASP-WIP- and Arp2/3-mediated actin nucleation...
September 18, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28916189/phosphoinositide-5-phosphatase-activities-control-cell-motility-in-glioblastoma-two-phosphoinositides-pi-4-5-p2-and-pi-3-4-p2-are-involved
#3
REVIEW
Ana Raquel Ramos, William's Elong Edimo, Christophe Erneux
Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes...
September 5, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28879546/the-btk-dependent-pip5k1%C3%AE-lipid-kinase-activation-by-fas-counteracts-fasl-induced-cell-death
#4
Aurélie Rossin, Nadia Lounnas, Jérôme Durivault, Giorgia Miloro, Laurent Gagnoux-Palacios, Anne-Odile Hueber
The Fas/FasL system plays a critical role in death by apoptosis and immune escape of cancer cells. The Fas receptor being ubiquitously expressed in tissues, its apoptotic-inducing function, initiated upon FasL binding, is tightly regulated by several negative regulatory mechanisms to prevent inappropriate cell death. One of them, involving the non-receptor tyrosine kinase Btk, was reported mainly in B cells and only poorly described. We report here that Btk negatively regulates, through its tyrosine kinase activity, the FasL-mediated cell death in epithelial cell lines from colon cancer origin...
September 6, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28871048/an-emerging-case-for-membrane-pore-formation-as-a-common-mechanism-for-the-unconventional-secretion-of-fgf2-and-il-1%C3%AE
#5
REVIEW
David Brough, Pablo Pelegrin, Walter Nickel
Extracellular proteins with important signalling roles in processes, such as inflammation and angiogenesis, are known to employ unconventional routes of protein secretion. Although mechanisms of unconventional protein secretion are beginning to emerge, the precise molecular details have remained elusive for the majority of cargo proteins secreted by unconventional means. Recent findings suggest that for two examples of unconventionally secreted proteins, interleukin 1β (IL-1β) and fibroblast growth factor 2 (FGF2), the common molecular principle of pore formation may be shared...
September 4, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28871046/loss-of-ocrl-increases-ciliary-pi-4-5-p2-in-oculocerebrorenal-syndrome-of-lowe
#6
Philipp P Prosseda, Na Luo, Biao Wang, Jorge A Alvarado, Yang Hu, Yang Sun
Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts and glaucoma, mental retardation, and proximal renal tubular dysfunction. Mutations in OCRL1, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5)P2, cause Lowe syndrome. Previously we showed that OCRL localizes to the primary cilium, which has a distinct membrane phospholipid composition, but disruption of phosphoinositides in the ciliary membrane poorly understood. Here we demonstrate that cilia from Lowe syndrome patient fibroblasts exhibit increased levels of PI(4,5)P2 and decreased levels of PI4P...
September 4, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28869677/fibroblasts-derived-from-patients-with-opsismodysplasia-display-ship2-specific-cell-migration-and-adhesion-defects
#7
Somadri Ghosh, Céline Huber, Quentin Siour, Sergio S Sousa, Michael Wright, Valérie Cormier-Daire, Christophe Erneux
The SH2 domain containing inositol phosphatase 2 (SHIP2) dephosphorylates PI(3,4,5)P3 to generate PI(3,4)P2, a lipid involved in the control of cell migration and adhesion. The INPPL1 gene that encodes SHIP2 has been found to be mutated in several cases of opsismodysplasia (OPS), a rare autosomal recessive chondrodysplasia characterized by growth plate defects and delayed bone maturation. Reported mutations often result in premature stop codons or missense mutations in SHIP2 catalytic domain. SHIP2 biochemical properties are known from studies in cancer cells; its role in endochondral ossification is unknown...
September 4, 2017: Human Mutation
https://www.readbyqxmd.com/read/28826490/g-protein-%C3%AE-%C3%AE-subunits-inhibit-trpm3-ion-channels-in-sensory-neurons
#8
Talisia Quallo, Omar Alkhatib, Clive Gentry, David A Andersson, Stuart Bevan
Transient receptor potential (TRP) ion channels in peripheral sensory neurons are functionally regulated by hydrolysis of the phosphoinositide PI(4,5)P2 and changes in the level of protein kinase mediated phosphorylation following activation of various G protein coupled receptors. We now show that the activity of TRPM3 expressed in mouse dorsal root ganglion (DRG) neurons is inhibited by agonists of the Gi-coupled µ opioid, GABA-B and NPY receptors. These agonist effects are mediated by direct inhibition of TRPM3 by Gβγ subunits, rather than by a canonical cAMP mediated mechanism...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28815958/arabidopsis-exo70a1-recruits-patellin3-to-the-cell-membrane-independent-of-its-role-as-exocyst-subunit
#9
Chengyun Wu, Lu Tan, Max van Hooren, Xiaoyun Tan, Feng Liu, Yan Li, Yanxue Zhao, Bingxuan Li, Qingchen Rui, Teun Munnik, Yiqun Bao
The exocyst is a well-known complex to tether vesicles at the cell membrane before fusion. Whether an individual subunit can execute a unique function is largely unknown. Using yeast-two-hybrid (Y2H) analysis, we found that EXO70A1 interacted with the GOLD domain of Patellin3 (PATL3). The direct EXO70A1-PATL3 interaction was supported by in vitro and in vivo experiments. In Arabidopsis, PATL3-GFP colocalized with EXO70A1 predominantly at the cell membrane, and PATL3 localization was insensitive to BFA and TryA23...
August 16, 2017: Journal of Integrative Plant Biology
https://www.readbyqxmd.com/read/28815523/endoplasmic-reticulum-plasma-membrane-crosstalk-mediated-by-the-extended-synaptotagmins
#10
Yasunori Saheki
The endoplasmic reticulum (ER) possesses multiplicity of functions including protein synthesis, membrane lipid biogenesis, and Ca(2+) storage and has broad localization throughout the cell. While the ER and most other membranous organelles are highly interconnected via vesicular traffic that relies on membrane budding and fusion reactions, the ER forms direct contacts with virtually all other membranous organelles, including the plasma membrane (PM), without membrane fusion. Growing evidence suggests that these contacts play major roles in cellular physiology, including the regulation of Ca(2+) homeostasis and signaling and control of cellular lipid homeostasis...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28809547/quantitative-evaluation-of-viral-protein-binding-to-phosphoinositide-receptors-and-pharmacological-inhibition
#11
Seong-Oh Kim, Joshua A Jackman, Menashe Elazar, Sang-Joon Cho, Jeffrey S Glenn, Nam-Joon Cho
There is significant interest in developing analytical methods to characterize molecular recognition events between proteins and phosphoinositides, which are a medically important class of carbohydrate-functionalized lipids. Within this scope, one area of high priority involves quantitatively evaluating drug candidates that pharmacologically inhibit protein-phosphoinositide interactions. As full-length proteins are often difficult to produce, establishing methods to study these interactions with shorter, bioactive peptides would be advantageous...
August 28, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28799166/the-molecular-mechanism-underlying-unconventional-secretion-of-fibroblast-growth-factor-2-from-tumour-cells
#12
REVIEW
Julia P Steringer, Walter Nickel
Fibroblast Growth Factor 2 (FGF2) is a potent cell survival factor involved in tumour-induced angiogenesis. FGF2 is secreted from cells through an unconventional secretory mechanism based upon direct translocation across the plasma membrane. The molecular mechanism underlying this process depends on a surprisingly small set of trans-acting factors that are physically associated with the plasma membrane. FGF2 membrane translocation is mediated by the ability of FGF2 to oligomerise and to insert into the plasma membrane in a PI(4,5)P2 -dependent manner...
August 10, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28793264/vesicle-docking-is-a-key-target-of-local-pi-4-5-p2-metabolism-in-the-secretory-pathway-of-ins-1-cells
#13
Chen Ji, Fan Fan, Xuelin Lou
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) signaling is transient and spatially confined in live cells. How this pattern of signaling regulates transmitter release and hormone secretion has not been addressed. We devised an optogenetic approach to control PI(4,5)P2 levels in time and space in insulin-secreting cells. Combining this approach with total internal reflection fluorescence microscopy, we examined individual vesicle-trafficking steps. Unlike long-term PI(4,5)P2 perturbations, rapid and cell-wide PI(4,5)P2 reduction in the plasma membrane (PM) strongly inhibits secretion and intracellular Ca(2+) concentration ([Ca(2+)]i) responses, but not sytaxin1a clustering...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28761175/rock1-is-a-novel-rac1-effector-to-regulate-tubular-endocytic-membrane-formation-during-clathrin-independent-endocytosis
#14
David Soriano-Castell, Albert Chavero, Carles Rentero, Marta Bosch, Maite Vidal-Quadras, Albert Pol, Carlos Enrich, Francesc Tebar
Clathrin-dependent and -independent pathways contribute for β1-integrin endocytosis. This study defines a tubular membrane clathrin-independent endocytic network, induced with the calmodulin inhibitor W13, for β1-integrin internalization. This pathway is dependent on increased phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) levels and dynamin activity at the plasma membrane. Exogenous addition of PI(4,5)P2 or phosphatidylinositol-4-phosphate 5-kinase (PIP5K) expression mimicked W13-generated-tubules which are inhibited by active Rac1...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722655/key-steps-in-unconventional-secretion-of-fibroblast-growth-factor-2-reconstituted-with-purified-components
#15
Julia P Steringer, Sascha Lange, Sabína Čujová, Radek Šachl, Chetan Poojari, Fabio Lolicato, Oliver Beutel, Hans-Michael Müller, Sebastian Unger, Ünal Coskun, Alf Honigmann, Ilpo Vattulainen, Martin Hof, Christian Freund, Walter Nickel
FGF2 is secreted from cells by an unconventional secretory pathway. This process is mediated by direct translocation across the plasma membrane. Here, we define the minimal molecular machinery required for FGF2 membrane translocation in a fully reconstituted inside-out vesicle system. FGF2 membrane translocation is thermodynamically driven by PI(4,5)P2-induced membrane insertion of FGF2 oligomers. The latter serve as dynamic translocation intermediates of FGF2 with a subunit number in the range of 8-12 FGF2 molecules...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28720663/direct-interaction-of-the-golgi-v-atpase-a-subunit-isoform-with-pi-4-p-drives-localization-of-golgi-v-atpases-in-yeast
#16
Subhrajit Banerjee, Patricia M Kane
Luminal pH and phosphoinositide content are fundamental features of organelle identity. Vacuolar H(+)-ATPases (V-ATPases) drive organelle acidification in all eukaryotes, and membrane-bound a-subunit isoforms of the V-ATPase are implicated in organelle-specific targeting and regulation. Earlier work demonstrated that the endolysosomal lipid PI(3,5)P2 activates V-ATPases containing the vacuolar a-subunit isoform in Saccharomyces cerevisiae Here we demonstrate that PI(4)P, the predominant Golgi phosphatidylinositol (PI) species, directly interacts with the cytosolic amino terminal (NT) domain of the yeast Golgi V-ATPase a-isoform Stv1...
September 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28710365/suppression-of-cell-migration-by-phospholipase-c-related-catalytically-inactive-protein-dependent-modulation-of-pi3k-signalling
#17
Satoshi Asano, Yuri Taniguchi, Yosuke Yamawaki, Jing Gao, Kae Harada, Hiroshi Takeuchi, Masato Hirata, Takashi Kanematsu
The metabolic processes of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] into PI(3,4,5)P3 and the subsequent PI(3,4,5)P3 signalling are involved in cell migration. Dysfunctions in the control of this pathway can cause human cancer cell migration and metastatic growth. Here we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a PI(4,5)P2-binding protein, regulates cancer cell migration. PRIP overexpression in MCF-7 and BT-549 human breast cancer cells inhibited cell migration in vitro and metastasis development in vivo...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28650469/a-compartmentalized-phosphoinositide-signaling-axis-at-cilia-is-regulated-by-inpp5e-to-maintain-cilia-and-promote-sonic-hedgehog-medulloblastoma
#18
S E Conduit, V Ramaswamy, M Remke, D N Watkins, B J Wainwright, M D Taylor, C A Mitchell, J M Dyson
Sonic Hedgehog (SHH) signaling at primary cilia drives the proliferation and progression of a subset of medulloblastomas, the most common malignant paediatric brain tumor. Severe side effects associated with conventional treatments and resistance to targeted therapies has led to the need for new strategies. SHH signaling is dependent on primary cilia for signal transduction suggesting the potential for cilia destabilizing mechanisms as a therapeutic target. INPP5E is an inositol polyphosphate 5-phosphatase that hydrolyses PtdIns(4,5)P2 and more potently, the phosphoinositide (PI) 3-kinase product PtdIns(3,4,5)P3...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28634262/rassf4-regulator-of-plasma-membrane-pi-4-5-p2
#19
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.
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28621027/aromatic-amino-acids-and-their-relevance-in-the-specificity-of-the-ph-domain
#20
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
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