Genomes and Genes
Summary: Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.
- Bianco A, Reghellin V, Donnici L, Fenu S, Alvarez R, Baruffa C, et al. Metabolism of phosphatidylinositol 4-kinase III?-dependent PI4P Is subverted by HCV and is targeted by a 4-anilino quinazoline with antiviral activity. PLoS Pathog. 2012;8:e1002576 pubmed publisher..This observation implies that HCV--by recruiting PI4KIII? in the RNA replication complex--hijacks PI4P metabolism, ultimately resulting in a markedly altered subcellular distribution of the PI4KIII? product. ..
- Ho C, Alghamdi T, Botelho R. Phosphatidylinositol-3,5-bisphosphate: no longer the poor PIP2. Traffic. 2012;13:1-8 pubmed publisher..Most interestingly, many PtdIns(3,5)P(2) regulators play simultaneous roles in its synthesis and turnover. ..
- Berger K, Kelly S, Jordan T, Tartell M, Randall G. Hepatitis C virus stimulates the phosphatidylinositol 4-kinase III alpha-dependent phosphatidylinositol 4-phosphate production that is essential for its replication. J Virol. 2011;85:8870-83 pubmed publisher..5 cells and from dually transfected 293T cells. In sum, these results suggest that HCV NS5A modulation of PI4KA-dependent PI4P production influences replication complex formation. ..
- Reiss S, Rebhan I, Backes P, Romero Brey I, Erfle H, Matula P, et al. Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment. Cell Host Microbe. 2011;9:32-45 pubmed publisher..Our analysis suggests that the direct activation of a lipid kinase by HCV NS5A contributes critically to the integrity of the membranous viral replication complex. ..
- Yates L, Lumb C, Brahme N, Zalyte R, Bird L, De Colibus L, et al. Structural and functional characterization of the kindlin-1 pleckstrin homology domain. J Biol Chem. 2012;287:43246-61 pubmed publisher..We suggest the physiological ligand of the kindlin-1 PH domain is most likely not an inositol phosphate but another phosphorylated species. ..
- Prasad A, Jia Y, Chakraborty A, Li Y, Jain S, Zhong J, et al. Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling. Nat Immunol. 2011;12:752-60 pubmed publisher..Our findings establish a role for InsP7 in signal transduction and provide a mechanism for modulating PtdIns(3,4,5)P3 signaling in neutrophils...
- Ikonomov O, Sbrissa D, Delvecchio K, Xie Y, Jin J, Rappolee D, et al. The phosphoinositide kinase PIKfyve is vital in early embryonic development: preimplantation lethality of PIKfyve-/- embryos but normality of PIKfyve+/- mice. J Biol Chem. 2011;286:13404-13 pubmed publisher..Our data also shed light on the known human disorder linked to PIKFYVE mutations. ..
- Manna P, Jain S. Decreased hepatic phosphatidylinositol-3,4,5-triphosphate (PIP3) levels and impaired glucose homeostasis in type 1 and type 2 diabetic rats. Cell Physiol Biochem. 2012;30:1363-70 pubmed publisher..PIP2 levels were unchanged. PIP3 is decreased, AKT phosphorylation downregulated, GLUT2 protein expression increased and glucose homeostasis altered in livers of type 1 and type 2 diabetic rats. ..
- Manna P, Jain S. Hydrogen sulfide and L-cysteine increase phosphatidylinositol 3,4,5-trisphosphate (PIP3) and glucose utilization by inhibiting phosphatase and tensin homolog (PTEN) protein and activating phosphoinositide 3-kinase (PI3K)/serine/threonine protein kina. J Biol Chem. 2011;286:39848-59 pubmed publisher..This study provides evidence for a molecular mechanism by which H(2)S or LC can up-regulate the insulin-signaling pathways essential for maintenance of glucose metabolism. ..
- Grainger D, Tavelis C, Ryan A, Hinchliffe K. Involvement of phosphatidylinositol 5-phosphate in insulin-stimulated glucose uptake in the L6 myotube model of skeletal muscle. Pflugers Arch. 2011;462:723-32 pubmed publisher..Our results are consistent with a role for insulin-stimulated PtdIns5P production in regulating glucose transport by promoting PI 3-kinase signalling. ..
- Petrie R, Gavara N, Chadwick R, Yamada K. Nonpolarized signaling reveals two distinct modes of 3D cell migration. J Cell Biol. 2012;197:439-55 pubmed publisher..Thus, the relative polarization of intracellular signaling identifies two distinct modes of 3D cell migration governed intrinsically by RhoA, ROCK, and myosin II and extrinsically by the elastic behavior of the 3D extracellular matrix...
- Jean S, Cox S, Schmidt E, Robinson F, Kiger A. Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling. Mol Biol Cell. 2012;23:2723-40 pubmed publisher..This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control...
- Santiago Tirado F, Legesse Miller A, Schott D, Bretscher A. PI4P and Rab inputs collaborate in myosin-V-dependent transport of secretory compartments in yeast. Dev Cell. 2011;20:47-59 pubmed publisher..Thus, we show that a coincidence detection mechanism coordinates inputs from PI4P and the appropriate Rab for secretory compartment transport. ..
- Santiago Tirado F, Bretscher A. Membrane-trafficking sorting hubs: cooperation between PI4P and small GTPases at the trans-Golgi network. Trends Cell Biol. 2011;21:515-25 pubmed publisher..In this review, we summarize the current understanding of how these lipids and GTPases regulate membrane trafficking directly, emphasizing the recent discoveries of phosphatidylinositol 4-phosphate functions at the trans-Golgi network. ..
- Erneux C, Elong Edimo W. When worlds collide: inositol pyrophosphates and phosphoinositides intersect at the plasma membrane. Biochem J. 2013;453:e3-4 pubmed publisher..Those findings reveal a mechanism for localized depletion of InsP6 and 5-InsP7 at the plasma membrane and further translocation of PtdIns(3,4,5)P3-binding PH-domain-containing proteins. ..
- Okamura Y, Dixon J. Voltage-sensing phosphatase: its molecular relationship with PTEN. Physiology (Bethesda). 2011;26:6-13 pubmed publisher..These similarities include the cytoplasmic phosphatase region, the phosphoinositide binding region, and the putative membrane interacting C2 domain. ..
- Liu J, Fukuda K, Xu Z, Ma Y, HIRBAWI J, Mao X, et al. Structural basis of phosphoinositide binding to kindlin-2 protein pleckstrin homology domain in regulating integrin activation. J Biol Chem. 2011;286:43334-42 pubmed publisher..Moreover, they shed light upon a mechanism as to how the PH domain mediates membrane engagement of kindlin-2 to promote its binding to integrin and cooperation with talin for regulation of integrin activation. ..
- Chen C, Wang Y, Sesaki H, Iijima M. Myosin I links PIP3 signaling to remodeling of the actin cytoskeleton in chemotaxis. Sci Signal. 2012;5:ra10 pubmed publisher..These data suggest a mechanism through which the PIP3 signal is transmitted through myosin I to the actin cytoskeleton. ..
- Endo Streeter S, Tsui M, Odom A, Block J, York J. Structural studies and protein engineering of inositol phosphate multikinase. J Biol Chem. 2012;287:35360-9 pubmed publisher..Overall, our studies provide new insights into the structure and function of IPMK and utilize a synthetic biological approach to redesign inositol phosphate signaling pathways. ..
- Erneux C, Edimo W, Deneubourg L, Pirson I. SHIP2 multiple functions: a balance between a negative control of PtdIns(3,4,5)P? level, a positive control of PtdIns(3,4)P? production, and intrinsic docking properties. J Cell Biochem. 2011;112:2203-9 pubmed publisher..These non-catalytic properties associated to a PI phosphatase have also been reported for other enzymes of the metabolism of myo-inositol such as Ins(1,4,5)P(3) 3-kinases, inositol phosphate multikinase (IPMK), or PTEN. ..
- Stefan C, Manford A, Baird D, Yamada Hanff J, Mao Y, Emr S. Osh proteins regulate phosphoinositide metabolism at ER-plasma membrane contact sites. Cell. 2011;144:389-401 pubmed publisher..Our findings further suggest that the conserved Osh proteins control PI metabolism at additional membrane contact sites. ..
- Zhang L, Hong Z, Lin W, Shao R, Goto K, Hsu V, et al. ARF1 and GBF1 generate a PI4P-enriched environment supportive of hepatitis C virus replication. PLoS ONE. 2012;7:e32135 pubmed publisher..Moreover, the vesicular transport proteins ARF1 and GBF1 colocalized with PI4KIII? and were both required for HCV replication. During authentic HCV infection, PI4P plays an integral role in virus replication. ..
- Lumb C, He J, Xue Y, Stansfeld P, Stahelin R, Kutateladze T, et al. Biophysical and computational studies of membrane penetration by the GRP1 pleckstrin homology domain. Structure. 2011;19:1338-46 pubmed publisher..This supports a "dual-recognition" model of binding, with specific GRP1-PH-PI(3,4,5)P(3) interactions supplemented by interactions of loop regions with the lipid bilayer. ..
- Wullschleger S, Wasserman D, Gray A, Sakamoto K, Alessi D. Role of TAPP1 and TAPP2 adaptor binding to PtdIns(3,4)P2 in regulating insulin sensitivity defined by knock-in analysis. Biochem J. 2011;434:265-74 pubmed publisher..These observations provide the first genetic evidence to support the notion that binding of TAPP1 and TAPP2 adap-tors to PtdIns(3,4)P(2) function as negative regulators of the insulin and PI3K signalling pathways. ..
- Silhankova M, Port F, Harterink M, Basler K, Korswagen H. Wnt signalling requires MTM-6 and MTM-9 myotubularin lipid-phosphatase function in Wnt-producing cells. EMBO J. 2010;29:4094-105 pubmed publisher..We conclude that regulation of endosomal trafficking by the MTM-6/MTM-9 myotubularin complex is required for the retromer-dependent recycling of MIG-14/Wls and Wnt secretion. ..
- Mesmin B, Bigay J, Moser von Filseck J, Lacas Gervais S, Drin G, Antonny B. A four-step cycle driven by PI(4)P hydrolysis directs sterol/PI(4)P exchange by the ER-Golgi tether OSBP. Cell. 2013;155:830-43 pubmed publisher..Other lipid transfer proteins are tethered by the same mechanism. Thus, OSBP-mediated back transfer of PI(4)P might coordinate the transfer of other lipid species at the ER-Golgi interface...
- de Saint Jean M, Delfosse V, Douguet D, Chicanne G, Payrastre B, Bourguet W, et al. Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers. J Cell Biol. 2011;195:965-78 pubmed publisher..Coupled to PI(4)P metabolism, this transport cycle would create sterol gradients. Because the residues that recognize PI(4)P are conserved in Osh4p homologues, other Osh/Orp are potential sterol/phosphoinositol phosphate exchangers. ..
- Jaber N, Dou Z, Chen J, Catanzaro J, Jiang Y, Ballou L, et al. Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function. Proc Natl Acad Sci U S A. 2012;109:2003-8 pubmed publisher..Taken together, our results indicate that Vps34 plays an essential role in regulating functional autophagy and is indispensable for normal liver and heart function. ..
- Waugh M, Chu K, Clayton E, Minogue S, Hsuan J. Detergent-free isolation and characterization of cholesterol-rich membrane domains from trans-Golgi network vesicles. J Lipid Res. 2011;52:582-9 pubmed publisher..We demonstrate that this technique can give useful insights into the compartmentation of phosphoinositide synthesis, and it facilitates the isolation of cholesterol-rich membranes from a population of TGN-trafficking vesicles. ..
- Alfonso Pecchio A, Cardozo Gizzi A, Renner M, Molina Calavita M, Caputto B. c-Fos activates and physically interacts with specific enzymes of the pathway of synthesis of polyphosphoinositides. Mol Biol Cell. 2011;22:4716-25 pubmed publisher..Both coimmunoprecipitation and fluorescence resonance energy transfer experiments consistently showed a physical interaction between the N-terminal domain of c-Fos and the enzymes it activates. ..
- Gokhale N, Zaremba A, Shears S. Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain. Biochem J. 2011;434:415-26 pubmed publisher..We have therefore demonstrated receptor-regulated compartmentalization of inositol pyrophosphate synthesis in mammalian cells. ..
- Li X, Wang X, Zhang X, Zhao M, Tsang W, Zhang Y, et al. Genetically encoded fluorescent probe to visualize intracellular phosphatidylinositol 3,5-bisphosphate localization and dynamics. Proc Natl Acad Sci U S A. 2013;110:21165-70 pubmed publisher..Our development of a PI(3,5)P2-specific probe may facilitate studies of both intracellular signal transduction and membrane trafficking in the endosomes and lysosomes. ..
- Wood C, Hung C, Huoh Y, Mousley C, Stefan C, BANKAITIS V, et al. Local control of phosphatidylinositol 4-phosphate signaling in the Golgi apparatus by Vps74 and Sac1 phosphoinositide phosphatase. Mol Biol Cell. 2012;23:2527-36 pubmed publisher..The results establish additive roles of Vps74-mediated and sphingolipid-dependent sorting of Golgi residents. ..
- Daboussi L, Costaguta G, Payne G. Phosphoinositide-mediated clathrin adaptor progression at the trans-Golgi network. Nat Cell Biol. 2012;14:239-48 pubmed publisher..Gga2p binds directly to the TGN PtdIns(4)-kinase Pik1p and contributes to Pik1p recruitment. These results identify a PtdIns(4)P-based mechanism for regulating progressive assembly of adaptor-specific clathrin coats at the TGN. ..
- Bishe B, Syed G, Field S, Siddiqui A. Role of phosphatidylinositol 4-phosphate (PI4P) and its binding protein GOLPH3 in hepatitis C virus secretion. J Biol Chem. 2012;287:27637-47 pubmed publisher..These studies establish the role of PI4P and its interacting protein GOLPH3 in HCV secretion and strengthen the significance of the Golgi secretory pathway in this process. ..
- Kano F, Arai T, Matsuto M, Hayashi H, Sato M, Murata M. Hydrogen peroxide depletes phosphatidylinositol-3-phosphate from endosomes in a p38 MAPK-dependent manner and perturbs endocytosis. Biochim Biophys Acta. 2011;1813:784-801 pubmed publisher..This article is part of a Special Issue entitled: 11th European Symposium on Calcium. ..
- Posor Y, Eichhorn Gruenig M, Puchkov D, Schöneberg J, Ullrich A, Lampe A, et al. Spatiotemporal control of endocytosis by phosphatidylinositol-3,4-bisphosphate. Nature. 2013;499:233-7 pubmed publisher..These findings provide a mechanistic framework for the role of PI(3,4)P2 in endocytosis and unravel a novel discrete function of PI(3,4)P2 in a central cell physiological process. ..
- Lu N, Shen Q, Mahoney T, Neukomm L, Wang Y, Zhou Z. Two PI 3-kinases and one PI 3-phosphatase together establish the cyclic waves of phagosomal PtdIns(3)P critical for the degradation of apoptotic cells. PLoS Biol. 2012;10:e1001245 pubmed publisher..They further shed light on how the temporally controlled reversible phosphorylation of phosphoinositides regulates the progression of multi-step cellular events...
- Miao B, Skidan I, Yang J, Lugovskoy A, Reibarkh M, Long K, et al. Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains. Proc Natl Acad Sci U S A. 2010;107:20126-31 pubmed publisher..Overall, our studies demonstrate the feasibility of developing specific small molecule antagonists of PIP3 signaling...
- Raiborg C, Schink K, Stenmark H. Class III phosphatidylinositol 3-kinase and its catalytic product PtdIns3P in regulation of endocytic membrane traffic. FEBS J. 2013;280:2730-42 pubmed publisher..Here we review the functions of key phosphatidylinositol 3-phosphate effectors in regulation of endocytic membrane dynamics and protein sorting...
- Li Z, Venable R, Rogers L, Murray D, Pastor R. Molecular dynamics simulations of PIP2 and PIP3 in lipid bilayers: determination of ring orientation, and the effects of surface roughness on a Poisson-Boltzmann description. Biophys J. 2009;97:155-63 pubmed publisher..These results support the utility of a rigid/flat bilayer model for PB-based studies of PIP2 and PIP3 as long as the orientations are judiciously chosen. ..
- 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. ..
- Burman C, Ktistakis N. Regulation of autophagy by phosphatidylinositol 3-phosphate. FEBS Lett. 2010;584:1302-12 pubmed publisher..In all of these settings, PI(3)P appears to create platforms that serve to recruit specific effectors for membrane trafficking events. In autophagy, PI(3)P may form the platform for autophagosome biogenesis. ..
- Spyridakis S, Leondaritis G, Nakos G, Lekka M, Galanopoulou D. A specific phospholipase C activity regulates phosphatidylinositol levels in lung surfactant of patients with acute respiratory distress syndrome. Am J Respir Cell Mol Biol. 2010;42:357-62 pubmed publisher..Thus, we have identified for the first time an extracellular PI-PLC enzyme activity that may be acutely involved in the regulation of PtdIns levels in LS. ..
- Garnier Lhomme M, Byrne R, Hobday T, Gschmeissner S, Woscholski R, Poccia D, et al. Nuclear envelope remnants: fluid membranes enriched in sterols and polyphosphoinositides. PLoS ONE. 2009;4:e4255 pubmed publisher..Based on their atypical biophysical characteristics and phospholipid composition, we suggest a possible role for nuclear envelope remnants in membrane fusion leading to nuclear envelope assembly. ..
- Cheong F, Sharma V, Blagoveshchenskaya A, Oorschot V, Brankatschk B, Klumperman J, et al. Spatial regulation of Golgi phosphatidylinositol-4-phosphate is required for enzyme localization and glycosylation fidelity. Traffic. 2010;11:1180-90 pubmed publisher..These results indicate that SAC1 organizes PI(4)P distribution between the Golgi complex and the TGN, which is instrumental for resident enzyme partitioning and Golgi morphology. ..