Genomes and Genes
Summary: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.
- Ludtmann M, Boeckeler K, Williams R. Molecular pharmacology in a simple model system: implicating MAP kinase and phosphoinositide signalling in bipolar disorder. Semin Cell Dev Biol. 2011;22:105-13 pubmed publisher..Analysis of the molecular pathways targeted by these drugs in Dictyostelium and translation of discoveries to animal systems has helped to further understand the molecular mechanisms of these bipolar disorder treatments. ..
- Balla T. Phosphoinositides: tiny lipids with giant impact on cell regulation. Physiol Rev. 2013;93:1019-137 pubmed publisher..This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease. ..
- Leondaritis G, Sarri T, Dafnis I, Efstathiou A, Galanopoulou D. Biochemical and genetic evidence for the presence of multiple phosphatidylinositol- and phosphatidylinositol 4,5-bisphosphate-specific phospholipases C in Tetrahymena. Eukaryot Cell. 2011;10:412-22 pubmed publisher..Our findings imply the presence of a conserved and elaborate PI-PLC-Ins(1,4,5)P(3)-Ca(2+) regulatory axis in ciliates...
- Piao H, Mayinger P. Growth and metabolic control of lipid signalling at the Golgi. Biochem Soc Trans. 2012;40:205-9 pubmed publisher..These results suggest that temporal and spatial integration of metabolic and lipid signalling networks at the Golgi is required for controlling the secretory pathway. ..
- Huang Y, Sauer K. Lipid signaling in T-cell development and function. Cold Spring Harb Perspect Biol. 2010;2:a002428 pubmed publisher..We propose that phosphoinositide lipids and soluble inositol phosphates (IPs) can act as complementary partners whose interplay could have broadly important roles in cellular signaling. ..
- Imae R, Inoue T, Kimura M, Kanamori T, Tomioka N, Kage Nakadai E, et al. Intracellular phospholipase A1 and acyltransferase, which are involved in Caenorhabditis elegans stem cell divisions, determine the sn-1 fatty acyl chain of phosphatidylinositol. Mol Biol Cell. 2010;21:3114-24 pubmed publisher..We propose that the sn-1 fatty acid of PI is determined by ipla-1 and acl-8, -9, -10 and crucial for asymmetric divisions. ..
- Ainge G, Compton B, Hayman C, Martin W, Toms S, Larsen D, et al. Chemical synthesis and immunosuppressive activity of dipalmitoyl phosphatidylinositol hexamannoside. J Org Chem. 2011;76:4941-51 pubmed publisher..PIM(6) (1) exhibited dendritic cell-dependent suppression of CD8(+) T cell expansion in a human mixed lymphocyte reaction consistent with the well established immunosuppressive activity of whole mycobacteria. ..
- Kim Y, Guzmán Hernández M, Balla T. A highly dynamic ER-derived phosphatidylinositol-synthesizing organelle supplies phosphoinositides to cellular membranes. Dev Cell. 2011;21:813-24 pubmed publisher..We propose a model in which PtdIns is synthesized in a highly mobile lipid distribution platform and is delivered to other membranes during multiple contacts by yet-to-be-defined lipid transfer mechanisms. ..
- Shewan A, Eastburn D, Mostov K. Phosphoinositides in cell architecture. Cold Spring Harb Perspect Biol. 2011;3:a004796 pubmed publisher..We place a special emphasis on highlighting recent studies demonstrating phosphoinositide regulation of epithelial cell polarity and how individual cells use phosphoinositides to further organize into epithelial tissues. ..
- Marée A, Grieneisen V, Edelstein Keshet L. How cells integrate complex stimuli: the effect of feedback from phosphoinositides and cell shape on cell polarization and motility. PLoS Comput Biol. 2012;8:e1002402 pubmed publisher..We explain these concepts in the context of several in silico experiments using our 2D computational cell model. ..
- Krick R, Busse R, Scacioc A, Stephan M, Janshoff A, Thumm M, et al. Structural and functional characterization of the two phosphoinositide binding sites of PROPPINs, a ?-propeller protein family. Proc Natl Acad Sci U S A. 2012;109:E2042-9 pubmed publisher..Our experiments show that PROPPINs contain two individual phosphoinositide binding sites. Based on docking studies, we propose a model for phosphoinositide binding of PROPPINs. ..
- Falkenburger B, Jensen J, Dickson E, Suh B, Hille B. Phosphoinositides: lipid regulators of membrane proteins. J Physiol. 2010;588:3179-85 pubmed publisher..In summary, phosphoinositides contribute to the selection of peripheral proteins for each membrane and regulate the activity of the integral proteins. ..
- Chen H, Xiong L. myo-Inositol-1-phosphate synthase is required for polar auxin transport and organ development. J Biol Chem. 2010;285:24238-47 pubmed publisher..mips1 mutants have significantly reduced levels of major phosphatidylinositols and exhibit much slower rates of endocytosis...
- Lee H, Kubo T, Kono N, Kage Nakadai E, Gengyo Ando K, Mitani S, et al. Depletion of mboa-7, an enzyme that incorporates polyunsaturated fatty acids into phosphatidylinositol (PI), impairs PI 3-phosphate signaling in Caenorhabditis elegans. Genes Cells. 2012;17:748-57 pubmed publisher..Finally, we showed that autophagic clearance of protein aggregates is impaired in mboa-7 mutants. Taken together, these results suggest that the PUFA chain in PI has a role in some PI3P signaling...
- Kawashima M, Iwamoto N, Kawaguchi Sakita N, Sugimoto M, Ueno T, Mikami Y, et al. High-resolution imaging mass spectrometry reveals detailed spatial distribution of phosphatidylinositols in human breast cancer. Cancer Sci. 2013;104:1372-9 pubmed publisher..Recent lipidomic approach has identified several phospholipids and phosphatidylinositols (PIs) are accumulated in breast cancer tissues and are therefore novel biomarker candidates...
- Nunez L, Jesch S, Gaspar M, Almaguer C, Villa Garcia M, Ruiz Noriega M, et al. Cell wall integrity MAPK pathway is essential for lipid homeostasis. J Biol Chem. 2008;283:34204-17 pubmed publisher..These results indicate that an intact cell wall integrity pathway is required for maintaining proper lipid homeostasis in yeast, especially when cells are grown in the absence of inositol. ..
- König S, Hoffmann M, Mosblech A, Heilmann I. Determination of content and fatty acid composition of unlabeled phosphoinositide species by thin-layer chromatography and gas chromatography. Anal Biochem. 2008;378:197-201 pubmed publisher..Described here is a cost-efficient and reliable alternative developed by adaptation of a combination of classic methods for lipid analysis, thin-layer chromatography and gas chromatography. ..
- Laketa V, Zarbakhsh S, Morbier E, Subramanian D, Dinkel C, Brumbaugh J, et al. Membrane-permeant phosphoinositide derivatives as modulators of growth factor signaling and neurite outgrowth. Chem Biol. 2009;16:1190-6 pubmed publisher..This work establishes membrane-permeant phosphoinositides as powerful tools to study PI3K signaling and directly demonstrates that 3-phosphorylated phosphoinositides are instrumental for neurite initiation. ..
- Clague M, Urbé S, de Lartigue J. Phosphoinositides and the endocytic pathway. Exp Cell Res. 2009;315:1627-31 pubmed publisher..The enzymatic generation of lipids serves as an amplification mechanism through which a wide variety of effector molecules can be recruited. ..
- Gassama Diagne A, Payrastre B. Phosphoinositide signaling pathways: promising role as builders of epithelial cell polarity. Int Rev Cell Mol Biol. 2009;273:313-43 pubmed publisher..In this chapter, essential determinants of epithelial polarity will be reviewed with a particular focus on metabolism and function of phosphoinositides. ..
- Ase A, Bernier L, Blais D, Pankratov Y, Séguéla P. Modulation of heteromeric P2X1/5 receptors by phosphoinositides in astrocytes depends on the P2X1 subunit. J Neurochem. 2010;113:1676-84 pubmed publisher..Our results suggest that the contribution of calcium-permeable heteromeric P2X1/5 receptor channels to the excitability of astrocytes is modulated by PI(4,5)P(2) through the P2X1 lipid-binding domain. ..
- Ischebeck T, Seiler S, Heilmann I. At the poles across kingdoms: phosphoinositides and polar tip growth. Protoplasma. 2010;240:13-31 pubmed publisher..The evolutionary conservation of the PI system among eukaryotic cells suggests a role for PIs in tip growing cells in models where PIs so far have not been a focus of attention, such as fungal hyphae. ..
- Jin N, Chow C, Liu L, Zolov S, Bronson R, Davisson M, et al. VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouse. EMBO J. 2008;27:3221-34 pubmed publisher..Moreover, these studies show that the association of Fab1 with the complex is essential for viability in the mouse. ..
- Guerin M, Kaur D, Somashekar B, Gibbs S, Gest P, Chatterjee D, et al. New insights into the early steps of phosphatidylinositol mannoside biosynthesis in mycobacteria: PimB' is an essential enzyme of Mycobacterium smegmatis. J Biol Chem. 2009;284:25687-96 pubmed publisher..The essentiality of these three enzymes emphasizes the interest of novel anti-tuberculosis drugs targeting the initial steps of PIM biosynthesis...
- Zoncu R, Perera R, Balkin D, Pirruccello M, Toomre D, De Camilli P. A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes. Cell. 2009;136:1110-21 pubmed publisher..These findings reveal a surprising plasticity of the early endocytic pathway. Importantly, PI3P functions as a switch to dynamically regulate maturation and signaling of APPL endosomes...
- Poteryaev D, Datta S, Ackema K, Zerial M, Spang A. Identification of the switch in early-to-late endosome transition. Cell. 2010;141:497-508 pubmed publisher..SAND-1/Mon1 thus acts as a switch by controlling the localization of RAB-5 and RAB-7 GEFs. ..
- Yaradanakul A, Wang T, Lariccia V, Lin M, Shen C, Liu X, et al. Massive Ca-induced membrane fusion and phospholipid changes triggered by reverse Na/Ca exchange in BHK fibroblasts. J Gen Physiol. 2008;132:29-50 pubmed publisher..In summary, our results provide no support for any regulatory or modulatory role of phospholipids in Ca-induced membrane fusion in fibroblasts. ..
- Meerschaert K, Tun M, Remue E, De Ganck A, Boucherie C, Vanloo B, et al. The PDZ2 domain of zonula occludens-1 and -2 is a phosphoinositide binding domain. Cell Mol Life Sci. 2009;66:3951-66 pubmed publisher..This study shows for the first time that ZO isoforms bind PtdInsPs and offers an alternative regulatory mechanism for the formation and stabilisation of protein complexes in the nucleus. ..
- McCrea H, De Camilli P. Mutations in phosphoinositide metabolizing enzymes and human disease. Physiology (Bethesda). 2009;24:8-16 pubmed publisher..Many such enzymes are attractive targets for therapeutic interventions. Here, we review diseases linked to inheritable or somatic mutations of these enzymes...
- Donahue J, Alford S, Torabinejad J, Kerwin R, Nourbakhsh A, Ray W, et al. The Arabidopsis thaliana Myo-inositol 1-phosphate synthase1 gene is required for Myo-inositol synthesis and suppression of cell death. Plant Cell. 2010;22:888-903 pubmed publisher..Thus, MIPS1 has a significant impact on myo-inositol levels that is critical for maintaining levels of ascorbic acid, phosphatidylinositol, and ceramides that regulate growth, development, and cell death. ..
- Manjithaya R, Nazarko T, Farre J, Subramani S. Molecular mechanism and physiological role of pexophagy. FEBS Lett. 2010;584:1367-73 pubmed publisher..These insights and additional observations in the literature provide a framework for an understanding of the physiological role(s) of pexophagy. ..
- Pu M, Roberts M, Gershenson A. Fluorescence correlation spectroscopy of phosphatidylinositol-specific phospholipase C monitors the interplay of substrate and activator lipid binding. Biochemistry. 2009;48:6835-45 pubmed publisher..These results provide a direct analysis of vesicle binding and catalytic activity and shed light on how occupation of the activator site enhances enzymatic activity. ..
- Mao Y, Balkin D, Zoncu R, Erdmann K, Tomasini L, Hu F, et al. A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism. EMBO J. 2009;28:1831-42 pubmed publisher..These findings suggest an evolutionary pressure for a specialized function of OCRL in bridging phosphoinositide metabolism to clathrin-dependent membrane trafficking. ..
- Korzeniowski M, Popovic M, Szentpetery Z, Varnai P, Stojilkovic S, Balla T. Dependence of STIM1/Orai1-mediated calcium entry on plasma membrane phosphoinositides. J Biol Chem. 2009;284:21027-35 pubmed publisher..These results suggest an inositide requirement of Orai1 activation but not STIM1 movements and indicate that PtdIns4P rather than PtdIns(4,5)P2 is a likely determinant of Orai1 channel activity. ..
- Boonyarattanakalin S, Liu X, Michieletti M, Lepenies B, Seeberger P. Chemical synthesis of all phosphatidylinositol mannoside (PIM) glycans from Mycobacterium tuberculosis. J Am Chem Soc. 2008;130:16791-9 pubmed publisher..Synthetic PIMs served as immune stimulators during immunization experiments in C57BL/6 mice when coupled to the model antigen keyhole-limpet hemocyanin (KLH). ..
- Sarkes D, Rameh L. A novel HPLC-based approach makes possible the spatial characterization of cellular PtdIns5P and other phosphoinositides. Biochem J. 2010;428:375-84 pubmed publisher..These results indicate that basal PtdIns5P and the PtdIns5P pathway for PtdIns(4,5)P(2) synthesis may play a role in Golgi-mediated vesicle trafficking. ..
- Doz E, Rose S, Court N, Front S, Vasseur V, Charron S, et al. Mycobacterial phosphatidylinositol mannosides negatively regulate host Toll-like receptor 4, MyD88-dependent proinflammatory cytokines, and TRIF-dependent co-stimulatory molecule expression. J Biol Chem. 2009;284:23187-96 pubmed publisher
- Schaaf G, Ortlund E, Tyeryar K, Mousley C, Ile K, Garrett T, et al. Functional anatomy of phospholipid binding and regulation of phosphoinositide homeostasis by proteins of the sec14 superfamily. Mol Cell. 2008;29:191-206 pubmed publisher..Collectively, these findings outline functional mechanisms for the Sec14 superfamily and reveal additional layers of complexity for regulating phosphoinositide homeostasis in eukaryotes. ..
- Carland F, Nelson T. CVP2- and CVL1-mediated phosphoinositide signaling as a regulator of the ARF GAP SFC/VAN3 in establishment of foliar vein patterns. Plant J. 2009;59:895-907 pubmed publisher..We propose that these two 5'-phosphatases regulate vein continuity and cell polarity by generating a specific PI ligand for SFC/VAN3. ..
- Heilmann I. Using genetic tools to understand plant phosphoinositide signalling. Trends Plant Sci. 2009;14:171-9 pubmed publisher..A detailed understanding of the functions and effects of PIs might offer new opportunities for modulating plant growth and hardiness against environmental influences. ..
- Driessen N, Ummels R, Maaskant J, Gurcha S, Besra G, Ainge G, et al. Role of phosphatidylinositol mannosides in the interaction between mycobacteria and DC-SIGN. Infect Immun. 2009;77:4538-47 pubmed publisher..Hence, we conclude that, like ManLAM, PIM(6) represents a bona fide DC-SIGN ligand but that other, as-yet-unknown, ligands dominate in the interaction between mycobacteria and DCs. ..
- Poccia D, Larijani B. Phosphatidylinositol metabolism and membrane fusion. Biochem J. 2009;418:233-46 pubmed publisher..These diverse roles underscore the importance of these phospholipids in the fusion of biological membranes. ..
- Skwarek L, Boulianne G. Great expectations for PIP: phosphoinositides as regulators of signaling during development and disease. Dev Cell. 2009;16:12-20 pubmed publisher..This review summarizes recent work on the role of phosphoinositides in developmental signaling and in a number of diseases and developmental disorders. ..
- Bankaitis V, Mousley C, Schaaf G. The Sec14 superfamily and mechanisms for crosstalk between lipid metabolism and lipid signaling. Trends Biochem Sci. 2010;35:150-60 pubmed publisher..Mechanisms of crosstalk, by which non-enzymatic proteins integrate metabolic cues with the action of interfacial enzymes, represent unappreciated regulatory themes in lipid signaling. ..
- Rhoades E, Archambault A, Greendyke R, Hsu F, Streeter C, Byrd T. Mycobacterium abscessus Glycopeptidolipids mask underlying cell wall phosphatidyl-myo-inositol mannosides blocking induction of human macrophage TNF-alpha by preventing interaction with TLR2. J Immunol. 2009;183:1997-2007 pubmed publisher..Conversely spontaneous "unmasking" of cell wall lipids may promote airway inflammation. ..
- Buccafusca R, Venditti C, Kenyon L, Johanson R, Van Bockstaele E, Ren J, et al. Characterization of the null murine sodium/myo-inositol cotransporter 1 (Smit1 or Slc5a3) phenotype: myo-inositol rescue is independent of expression of its cognate mitochondrial ribosomal protein subunit 6 (Mrps6) gene and of phosphatidylinositol le. Mol Genet Metab. 2008;95:81-95 pubmed publisher..In conclusion, in neonatal brain tissue, Mrps6 gene expression may not be contingent on function of its embedded Slc5a3 gene, while inositide deficiency may not be the mechanism of lethal apnea in null Slc5a3 mice. ..
- Mastronicolis S, Arvanitis N, Karaliota A, Magiatis P, Heropoulos G, Litos C, et al. Coordinated regulation of cold-induced changes in fatty acids with cardiolipin and phosphatidylglycerol composition among phospholipid species for the food pathogen Listeria monocytogenes. Appl Environ Microbiol. 2008;74:4543-9 pubmed publisher..Phosploaminolipid (19.9%) and phosphatidylinositol, (9.1%) are significantly different, containing significant amounts of straight-chain FA. These findings are supported by nuclear magnetic resonance analysis. ..
- Balla T, Szentpetery Z, Kim Y. Phosphoinositide signaling: new tools and insights. Physiology (Bethesda). 2009;24:231-44 pubmed publisher..The recent progress allows us to understand the underlying causes of certain human diseases and design new strategies for therapeutic interventions. ..
- Bernier L, Ase A, Chevallier S, Blais D, Zhao Q, Boué Grabot E, et al. Phosphoinositides regulate P2X4 ATP-gated channels through direct interactions. J Neurosci. 2008;28:12938-45 pubmed publisher..These results demonstrate novel regulatory roles of the major signaling phosphoinositides PIP(2) and PIP(3) on P2X(4) function through direct channel-lipid interactions. ..
- Nicot A, Laporte J. Endosomal phosphoinositides and human diseases. Traffic. 2008;9:1240-9 pubmed publisher..This review presents the roles of the endosomal PIs and their regulators and proposes defects of membrane remodeling as a common pathological mechanism for the corresponding diseases. ..