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Nihon Yakurigaku Zasshi. Folia... Apr 1995The most popular method for determining phosphoinositide hydrolysis is the analysis of water-soluble materials in cells or tissues that have been labeled with... (Review)
Review
The most popular method for determining phosphoinositide hydrolysis is the analysis of water-soluble materials in cells or tissues that have been labeled with [3H]inositol by separating them on anion exchange open columns or HPLC columns. Recently, a radioreceptor assay has become available for the analysis of inositol 1,4,5-trisphosphate (IP3) using IP3 receptors and [3H]IP3; this allows the analysis of IP3 in vivo. On the other hand, radiolabeled phosphoinositides are measured by thin layer chromatography to analyze the breakdown or synthesis of phosphoinositide in response to stimuli. The purified enzyme with phospholipid vesicles can be used to hydrolyze [3H]phosphatidylinositol 4,5-bisphosphate (PIP2) to [3H]IP3, which makes it possible to search for direct action of a drug on phospholipase C.
Topics: Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Humans; Hydrolysis; Phosphatidylinositols; Radioligand Assay
PubMed: 7774856
DOI: 10.1254/fpj.105.191 -
Yakubutsu, Seishin, Kodo = Japanese... Jun 1991Inositol lipid plays a major role in cell signaling by functioning as precursors of second messengers. Phosphatidylinositol 4,5-bisphosphate, which is found in the... (Review)
Review
Inositol lipid plays a major role in cell signaling by functioning as precursors of second messengers. Phosphatidylinositol 4,5-bisphosphate, which is found in the plasma membrane, is hydrolyzed to give diacylglycerol and inositol 1,4,5-triphosphate. Diacylglycerol stimulates protein kinase C. Inositol 1,4,5-triphosphate releases calcium. Lithium inhibits the final dephosphorylation step and reduces the free inositol. This mechanism may explain the teratogenic effects of lithium. It seems that the effect of various antidepressants appear through the PI response.
Topics: Animals; Antidepressive Agents; Calcium; Diglycerides; Hydrolysis; Inositol 1,4,5-Trisphosphate; Lithium; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Phosphorylation; Protein Kinase C; Second Messenger Systems
PubMed: 1663305
DOI: No ID Found -
Tanpakushitsu Kakusan Koso. Protein,... Sep 2007
Review
Topics: Animals; Calcium; Cell Membrane; Cytoskeleton; GRB2 Adaptor Protein; Phosphatidylinositols; Protein Structure, Tertiary; Signal Transduction; Type C Phospholipases; Wiskott-Aldrich Syndrome Protein Family; Wiskott-Aldrich Syndrome Protein, Neuronal
PubMed: 17972419
DOI: No ID Found -
Biochimica Et Biophysica Acta Dec 1992Dimyristoylphosphatidylinositol (DMPI) has been synthesized with the appropriate natural stereochemistry and labelled with deuterium at specific sites in the... (Review)
Review
Dimyristoylphosphatidylinositol (DMPI) has been synthesized with the appropriate natural stereochemistry and labelled with deuterium at specific sites in the D-myo-inositol headgroup. 2H-NMR spectroscopy of DMPI in its lamellar phase at a molar ratio of water-to-lipid RW/L of 129 and at 70 degrees C reveals quadrupolar splittings delta v of 3.83 and 2.17 kHz, respectively, for the five axially oriented C-D bonds and the single equatorially oriented C-D bond of the D-myo-inositol headgroup. Between RW/L ratios of 129 and 210 and between 30 degrees C and 80 degrees C the value of the ratio of these splittings delta nu ax/delta nu eq varies significantly (between 1.17 and 4.38). If it is assumed that, at a particular temperature, there is a single preferred orientation of the inositol headgroup, and that motion of the DPMI molecule establishes axial symmetry with respect to the bilayer normal then the ratio of these quadrupolar splittings can be used to impose constraints on that orientation. For example, the data are inconsistent with a situation in which the inositol ring lies parallel to the membrane surface and are difficult to reconcile with an arrangement where the inositol ring lies perpendicular to the surface. Computational modelling identifies four possible 'tilted' orientations, all of which are consistent with the data, and two of these allow good intramolecular hydrogen bonds to be formed. In one there is hydrogen bonding between the inositol C2-OH and the phosphate pro-R oxygen. This is close to the conformation previously identified as being dominant in DMSO solution (Bushby, R.J., Byard, S.J., Hansbro, P.M. and Reid, D.G. (1990) Biochim. Biophys. Acta 1044, 231-236).
Topics: Chemical Phenomena; Chemistry, Physical; Deuterium; Hydrogen Bonding; Lipid Bilayers; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Phosphatidylinositols
PubMed: 1457451
DOI: 10.1016/0005-2736(92)90391-x -
Angewandte Chemie (International Ed. in... Sep 2021We synthesized the first multifunctionalized phosphoinositide polyphosphate derivatives featuring a photo-removable protecting group ("cage"), a photo-crosslinkable...
We synthesized the first multifunctionalized phosphoinositide polyphosphate derivatives featuring a photo-removable protecting group ("cage"), a photo-crosslinkable diazirine group, and a terminal alkyne group useful for click chemistry. We demonstrate that the lipid derivatives readily enter cells. After photo-crosslinking, cell fixation and fluorescent tagging via click chemistry, we determined the intracellular location of the lipid derivatives before and after uncaging of the lipids. We find that there is rapid trafficking of PI(3,4)P and PI(3,4,5)P derivatives to the plasma membrane, opening the intriguing possibility that there is active transport of these lipids involved. We employed the photo-crosslinking and click chemistry functions to analyze the proteome of PI(3,4,5)P -binding proteins. From the latter, we validated by RNAi that the putative lipid binding proteins ATP11A and MPP6 are involved in the transport of PI(3,4,5)P to the plasma membrane.
Topics: HeLa Cells; Humans; Molecular Structure; Phosphatidylinositols; Polyphosphates
PubMed: 34075669
DOI: 10.1002/anie.202103599 -
Biochemical Society Transactions May 1993
Review
Topics: Calcium; Erythrocyte Membrane; Humans; Lipid Bilayers; Magnesium; Membrane Lipids; Phosphatidic Acids; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositol Phosphates; Phosphatidylinositols
PubMed: 8395420
DOI: 10.1042/bst0210253 -
Handbook of Experimental Pharmacology 2020Despite interest in phosphoinositide (PtdIns) kinases, such as PtdIns 3 kinases (PI3K), as targets for controlling plasma membrane PtdIns levels in disease, the PtdIns... (Review)
Review
Despite interest in phosphoinositide (PtdIns) kinases, such as PtdIns 3 kinases (PI3K), as targets for controlling plasma membrane PtdIns levels in disease, the PtdIns have another less well-known site of action in the cell nucleus.Recent studies show that PtdIns use a variety of strategies to alter DNA responses. Here, we provide an overview of these newly identified forms of gene expression control, which should be considered when studying the therapeutic use of PtdIns-directed compounds. As PI3K is one of the most important clinical targets in recent years, we will focus on two polyphosphoinositides, the PI3K substrate PtdIns(4,5)di-phosphate (PI4,5P) and its product PtdIns(3,4,5)tri-phosphate (PI3,4,5P).
Topics: Cell Membrane; Cell Nucleus; Humans; Phosphatidylinositol 3-Kinases; Phosphatidylinositol Phosphates; Phosphatidylinositols
PubMed: 31201558
DOI: 10.1007/164_2019_219 -
The Journal of Organic Chemistry Jul 2007Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been identified as an important class of glycolipids with significant immune modulating...
Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been identified as an important class of glycolipids with significant immune modulating properties. We present here the syntheses of phosphatidylinositol dimannoside ether analogues 2 and 3 and evaluate their interleukin-12 (IL-12)-inducing properties along with dipalmitoyl PIM2 (1) in an in vitro bovine dendritic cell assay. Both synthetic PIM analogues and synthetic dipalmitoyl PIM2 (1) were effective at enhancing IL-12 production by immature bovine dendritic cells. Unexpectedly, ether analogue 2 was significantly more active than dipalmitoyl PIM2 (1) which indicates that modified PIM compounds can be strongly immunoactive and may have significant adjuvant activities.
Topics: Animals; Cattle; Cells, Cultured; Dendritic Cells; Interleukin-12; Molecular Structure; Phosphatidylinositols
PubMed: 17559276
DOI: 10.1021/jo070639m -
Annual Review of Plant Biology 2012"All things flow and change…even in the stillest matter there is unseen flux and movement." Attributed to Heraclitus (530-470 BC), from The Story of Philosophy by Will... (Review)
Review
"All things flow and change…even in the stillest matter there is unseen flux and movement." Attributed to Heraclitus (530-470 BC), from The Story of Philosophy by Will Durant. Heraclitus, a Greek philosopher, was thinking on a much larger scale than molecular signaling; however, his visionary comments are an important reminder for those studying signaling today. Even in unstimulated cells, signaling pathways are in constant metabolic flux and provide basal signals that travel throughout the organism. In addition, negatively charged phospholipids, such as the polyphosphorylated inositol phospholipids, provide a circuit board of on/off switches for attracting or repelling proteins that define the membranes of the cell. This template of charged phospholipids is sensitive to discrete changes and metabolic fluxes-e.g., in pH and cations-which contribute to the oscillating signals in the cell. The inherent complexities of a constantly fluctuating system make understanding how plants integrate and process signals challenging. In this review we discuss one aspect of lipid signaling: the inositol family of negatively charged phospholipids and their functions as molecular sensors and regulators of metabolic flux in plants.
Topics: Cell Nucleus; Humans; Light; Phosphatidylinositol Phosphates; Phosphatidylinositols; Phosphorylation; Plant Development; Signal Transduction
PubMed: 22404474
DOI: 10.1146/annurev-arplant-042110-103840 -
Molecular Biology of the Cell Mar 2000Yeast vacuoles undergo cycles of fragmentation and fusion as part of their transmission to the daughter cell and in response to changes of nutrients and the environment....
Yeast vacuoles undergo cycles of fragmentation and fusion as part of their transmission to the daughter cell and in response to changes of nutrients and the environment. Vacuole fusion can be reconstituted in a cell free system. We now show that the vacuoles synthesize phosphoinositides during in vitro fusion. Of these phosphoinositides, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) are important for fusion. Monoclonal antibodies to PI(4,5)P(2), neomycin (a phosphoinositide ligand), and phosphatidylinositol-specific phospholipase C interfere with the reaction. Readdition of PI(4, 5)P(2) restores fusion in each case. Phosphatidylinositol 3-phosphate and PI(3,5)P(2) synthesis are not required. PI(4,5)P(2) is necessary for priming, i.e., for the Sec18p (NSF)-driven release of Sec17p (alpha-SNAP), which activates the vacuoles for subsequent tethering and docking. Therefore, it represents the kinetically earliest requirement identified for vacuole fusion so far. Furthermore, PI(4,5)P(2) is required at a step that can only occur after docking but before the BAPTA sensitive step in the latest stage of the reaction. We hence propose that PI(4,5)P(2) controls two steps of vacuole fusion.
Topics: Membrane Fusion; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Saccharomyces cerevisiae; Vacuoles
PubMed: 10712501
DOI: 10.1091/mbc.11.3.807