Genomes and Genes
5 diphosphate phosphatidylinositol 4
Summary: A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)
- Otsuguro K, Tang J, Tang Y, Xiao R, Freichel M, Tsvilovskyy V, et al. Isoform-specific inhibition of TRPC4 channel by phosphatidylinositol 4,5-bisphosphate. J Biol Chem. 2008;283:10026-36 pubmed publisher..Thus, TRPC4 channels integrate a variety of G-protein-dependent stimuli, including a PIP(2)/cytoskeleton dependence reminiscent of the TRPC4-like muscarinic agonist-activated cation channels in ileal myocytes. ..
- 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. ..
- Bielas S, Silhavy J, Brancati F, Kisseleva M, Al Gazali L, Sztriha L, et al. Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nat Genet. 2009;41:1032-6 pubmed publisher..These data link PtdIns signaling to the primary cilium, a cellular structure that is becoming increasingly recognized for its role in mediating cell signals and neuronal function. ..
- Szentpetery Z, Balla A, Kim Y, Lemmon M, Balla T. Live cell imaging with protein domains capable of recognizing phosphatidylinositol 4,5-bisphosphate; a comparative study. BMC Cell Biol. 2009;10:67 pubmed publisher..These studies also demonstrated that similar changes in PtdIns(4,5)P2 levels in the plasma membrane can differentially regulate multiple effectors if they display different affinities to PtdIns(4,5)P2. ..
- Yoshida S, Bartolini S, Pellman D. Mechanisms for concentrating Rho1 during cytokinesis. Genes Dev. 2009;23:810-23 pubmed publisher..These findings comprehensively define the targeting mechanisms of Rho1 essential for cytokinesis in yeast, and are likely to be relevant to cytokinesis in other organisms. ..
- Yakir Tamang L, Gerst J. A phosphatidylinositol-transfer protein and phosphatidylinositol-4-phosphate 5-kinase control Cdc42 to regulate the actin cytoskeleton and secretory pathway in yeast. Mol Biol Cell. 2009;20:3583-97 pubmed publisher..Based upon these findings, we propose that the exocytic signal involves PI delivery to the PI kinases (i.e., Mss4) by Sfh5, generation of PI(4,5)P(2), and PI(4,5)P(2)-dependent regulation of Cdc42 and the actin cytoskeleton. ..
- Song Y, Massart C, Chico Galdo V, Jin L, de Maertelaer V, DeCoster C, et al. Species specific thyroid signal transduction: conserved physiology, divergent mechanisms. Mol Cell Endocrinol. 2010;319:56-62 pubmed publisher..Thus although the physiological result of TSH action is the same in all species, the signaling pathways used are different. Other distinctions in signaling are observed such as the relative effects of one cascade on the other. ..
- Inanobe A, Nakagawa A, Matsuura T, Kurachi Y. A structural determinant for the control of PIP2 sensitivity in G protein-gated inward rectifier K+ channels. J Biol Chem. 2010;285:38517-23 pubmed publisher..The conservation of these residues within the K(G) channel family indicates that the ionic bond is a character that maintains the channels in a closed state by controlling the PIP(2) sensitivity. ..
- Kullmann P, Horn J. Homeostatic regulation of M-current modulates synaptic integration in secretomotor, but not vasomotor, sympathetic neurons in the bullfrog. J Physiol. 2010;588:923-38 pubmed publisher..Absence of this regulation in vasomotor neurons suggests a different integrative function, where synaptic gain increases in proportion to presynaptic activity. ..
- Dharmalingam E, Haeckel A, Pinyol R, Schwintzer L, Koch D, Kessels M, et al. F-BAR proteins of the syndapin family shape the plasma membrane and are crucial for neuromorphogenesis. J Neurosci. 2009;29:13315-27 pubmed publisher..Our data thus reveal that syndapin I is crucial for neuromorphogenesis and that different N-WASP activators ensure fine control of N-WASP activity and have distinct functions during neuronal network formation. ..
- Liu J, Sun Y, Drubin D, Oster G. The mechanochemistry of endocytosis. PLoS Biol. 2009;7:e1000204 pubmed publisher..The combination of experiments and theory in this work suggest a unified mechanism for endocytic vesicle formation across eukaryotes...
- Gallego Sandín S, Rodríguez García A, Alonso M, Garcia Sancho J. The endoplasmic reticulum of dorsal root ganglion neurons contains functional TRPV1 channels. J Biol Chem. 2009;284:32591-601 pubmed publisher..The low sensitivity of TRPV1(ER) to agonists may be critical for neuron health, because otherwise Ca(2+) depletion of ER could lead to ER stress, unfolding protein response, and cell death. ..
- D Avanzo N, Cheng W, Doyle D, Nichols C. Direct and specific activation of human inward rectifier K+ channels by membrane phosphatidylinositol 4,5-bisphosphate. J Biol Chem. 2010;285:37129-32 pubmed publisher..This raises the interesting hypothesis that PIP(2) activation of eukaryotic channels reflects an evolutionary adaptation of the channel to the appearance of PIP(2) in the eukaryotic cell membrane. ..
- Forcato D, Posada V, Beaugé L, Berberián G. Optimal metabolic regulation of the mammalian heart Na(+)/Ca(2+) exchanger requires a spacial arrangements with a PtdIns(4)-5kinase. Biochem Biophys Res Commun. 2010;402:147-52 pubmed publisher..This kind of supramolecular structure is needed to optimize binding of the newly synthesized PtdIns-4,5P2 to its target region in the exchanger protein. ..
- Pattnaik B, Hughes B. Regulation of Kir channels in bovine retinal pigment epithelial cells by phosphatidylinositol 4,5-bisphosphate. Am J Physiol Cell Physiol. 2009;297:C1001-11 pubmed publisher..We conclude that the activity of Kir channels in the RPE is critically dependent on the regeneration of membrane PIP2 by PI4 kinases and that this may explain the dependence of these channels on hydrolyzable ATP. ..
- Nawaz S, Kippert A, Saab A, Werner H, Lang T, Nave K, et al. Phosphatidylinositol 4,5-bisphosphate-dependent interaction of myelin basic protein with the plasma membrane in oligodendroglial cells and its rapid perturbation by elevated calcium. J Neurosci. 2009;29:4794-807 pubmed publisher..Together, these results establish that PIP2 is an essential determinant for stable membrane binding of MBP and provide a novel link between glial phosphoinositol metabolism and MBP function in development and disease. ..
- Radhakrishnan A, Stein A, Jahn R, Fasshauer D. The Ca2+ affinity of synaptotagmin 1 is markedly increased by a specific interaction of its C2B domain with phosphatidylinositol 4,5-bisphosphate. J Biol Chem. 2009;284:25749-60 pubmed publisher..Together, our findings lend support to the view that synaptotagmin functions by binding in a trans configuration whereby the C2A domain binds to the synaptic vesicle and the C2B binds to the PI(4,5)P2-enriched plasma membrane. ..
- Saltel F, Mortier E, Hytönen V, Jacquier M, Zimmermann P, Vogel V, et al. New PI(4,5)P2- and membrane proximal integrin-binding motifs in the talin head control beta3-integrin clustering. J Cell Biol. 2009;187:715-31 pubmed publisher..This interaction shields the beta-integrin tail from reassociation with its alpha subunit, thereby maintaining the integrin in a substrate-binding and clustering-competent form. ..
- Xing J, Strange K. Phosphatidylinositol 4,5-bisphosphate and loss of PLCgamma activity inhibit TRPM channels required for oscillatory Ca2+ signaling. Am J Physiol Cell Physiol. 2010;298:C274-82 pubmed publisher..PIP(2)-dependent regulation of GON-2/GTL-1 may provide a mechanism to coordinate plasma membrane Ca(2+) influx with PLCgamma and IP(3) receptor activity as well as intracellular Ca(2+) store depletion. ..
- Wigoda N, Ma X, Moran N. Phosphatidylinositol 4,5-bisphosphate regulates plant K(+) channels. Biochem Soc Trans. 2010;38:705-9 pubmed publisher..The present mini-review summarizes the experimentally demonstrated effects of PtdIns(4,5)P(2) on plant K(+) channels and examines their structure for candidate sites of direct PtdIns(4,5)P(2)-protein interaction. ..
- Dannemann N, Hart J, Ueno L, Vogt P. Phosphatidylinositol 4,5-bisphosphate-specific AKT1 is oncogenic. Int J Cancer. 2010;127:239-44 pubmed publisher..Gain-of-function mutants of AKT1 may not be affected by PI3K inhibitors that are currently in development. Therefore, AKT1 remains a distinct and important cancer target. ..
- Epshtein Y, Chopra A, Rosenhouse Dantsker A, Kowalsky G, Logothetis D, Levitan I. Identification of a C-terminus domain critical for the sensitivity of Kir2.1 to cholesterol. Proc Natl Acad Sci U S A. 2009;106:8055-60 pubmed publisher..These findings provide insights into the structural determinants of the sensitivity of Kir2 channels to cholesterol, and introduce the critical role of the cytosolic domain in cholesterol dependent channel regulation. ..
- 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. ..
- de Groot T, Lee K, Langeslag M, Xi Q, Jalink K, Bindels R, et al. Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation. J Am Soc Nephrol. 2009;20:1693-704 pubmed publisher..In summary, PTH activates the cAMP-PKA signaling cascade, which rapidly phosphorylates threonine-709 of TRPV5, increasing the channel's open probability and promoting Ca(2+) reabsorption in the distal nephron. ..
- Mendonsa R, Engebrecht J. Phosphatidylinositol-4,5-bisphosphate and phospholipase D-generated phosphatidic acid specify SNARE-mediated vesicle fusion for prospore membrane formation. Eukaryot Cell. 2009;8:1094-105 pubmed publisher..These data suggest that PLD-generated PA and PI(4,5)P(2) collaborate at multiple levels to promote SNARE-mediated fusion for PSM formation. ..
- Luo R, Ha V, Hayashi R, Randazzo P. Arf GAP2 is positively regulated by coatomer and cargo. Cell Signal. 2009;21:1169-79 pubmed publisher..Based on the common regulatory features of Arf GAP1 and 2, we propose a mechanism for cargo selection in which GTP hydrolysis triggered by cargo binding to the coat protein is coupled to coat polymerization. ..
- ..Recent work by our lab and others started to reveal a molecular mechanism by which HIV ensures to make the plasma membrane as a primary site of virus assembly. ..
- Carvalho K, Khalifat N, Maniti O, Nicolas C, Arold S, Picart C, et al. Phosphatidylinositol 4,5-bisphosphate-induced conformational change of ezrin and formation of ezrin oligomers. Biochemistry. 2010;49:9318-27 pubmed publisher..These oligomers had previously been observed in vivo, but their role is yet to be clarified. Our finding hints at a possible role for PIP? in the formation of ezrin oligomers. ..
- Zhang J, Luo R, Wu H, Wei S, Han W, Li G. Role of type Ialpha phosphatidylinositol-4-phosphate 5-kinase in insulin secretion, glucose metabolism, and membrane potential in INS-1 beta-cells. Endocrinology. 2009;150:2127-35 pubmed publisher..Taken together, our data suggest that PIP5K-Ialpha may play an important role in both the proximal and distal steps of signaling cascade for insulin secretion in beta-cells. ..
- Murray D, Tamm L. Clustering of syntaxin-1A in model membranes is modulated by phosphatidylinositol 4,5-bisphosphate and cholesterol. Biochemistry. 2009;48:4617-25 pubmed publisher..Possible implications of these results to the regulation of SNARE-mediated membrane fusion are discussed. ..
- Ponce Balbuena D, Lopez Izquierdo A, Ferrer T, Rodríguez Menchaca A, Aréchiga Figueroa I, Sanchez Chapula J. Tamoxifen inhibits inward rectifier K+ 2.x family of inward rectifier channels by interfering with phosphatidylinositol 4,5-bisphosphate-channel interactions. J Pharmacol Exp Ther. 2009;331:563-73 pubmed publisher..The data strongly suggest that tamoxifen, its metabolite, and the estrogen receptor inhibitor raloxifene inhibit Kir2.x channels indirectly by interfering with the interaction between the channel and PIP(2). ..
- Panchal N, Gaffney P. Synthesis of unsaturated phosphatidylinositol 4,5-bisphosphate and analogues. Org Biomol Chem. 2009;7:4832-41 pubmed publisher..A xanthenylidene acetal was used for key temporary protection of the 4,5-diol, and the 6-O was protected with a 1-(4-chlorophenyl)-4-ethoxypiperidin-4-yl (Cpep) acetal. ..
- ..Anionic lipids affect the function of many channels, including connexins, as shown in a recent report in BMC Biology. These effects might follow from direct binding of the anionic lipids to the channels...
- 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. ..
- Wu J, McNicholas C, Bevensee M. Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates the electrogenic Na/HCO3 cotransporter NBCe1-A expressed in Xenopus oocytes. Proc Natl Acad Sci U S A. 2009;106:14150-5 pubmed publisher..Spermine, poly-D-lysine, and neomycin all reduced the baseline HCO(3)(-)-induced inward currents by as much as 85%. In summary, PIP(2) stimulates NBCe1-A activity, and phosphoinositides are regulators of bicarbonate transporters. ..
- Lyall V, Phan T, Ren Z, Mummalaneni S, Melone P, Mahavadi S, et al. Regulation of the putative TRPV1t salt taste receptor by phosphatidylinositol 4,5-bisphosphate. J Neurophysiol. 2010;103:1337-49 pubmed publisher..e., the TRPV1 ion channel or its taste receptor variant, TRPV1t. ..
- Patsoukis N, Lafuente E, Meraner P, Kim J, Dombkowski D, Li L, et al. RIAM regulates the cytoskeletal distribution and activation of PLC-gamma1 in T cells. Sci Signal. 2009;2:ra79 pubmed publisher..Thus, by regulating the localization of PLC-gamma1, RIAM plays a central role in TCR signaling and the transcription of target genes. ..
- Wojtovich A, Williams D, Karcz M, Lopes C, Gray D, NEHRKE K, et al. A novel mitochondrial K(ATP) channel assay. Circ Res. 2010;106:1190-6 pubmed publisher..2 than the K(IR)6.1 isoform. The effect of fluoxetine on mK(ATP)-dependent cardioprotection has implications for the growing use of antidepressants in patients who may benefit from preconditioning. ..
- Szentpetery Z, Varnai P, Balla T. Acute manipulation of Golgi phosphoinositides to assess their importance in cellular trafficking and signaling. Proc Natl Acad Sci U S A. 2010;107:8225-30 pubmed publisher..This unique approach will allow further studies on the role of phosphoinositides in endocytic compartments that have evaded detection using the conventional long-term manipulations of inositide kinase and phosphatase activities. ..
- Yamaguchi H, Yoshida S, Muroi E, Kawamura M, Kouchi Z, Nakamura Y, et al. Phosphatidylinositol 4,5-bisphosphate and PIP5-kinase Ialpha are required for invadopodia formation in human breast cancer cells. Cancer Sci. 2010;101:1632-8 pubmed publisher..These results indicate that localized production of PI(4,5)P(2) by PIP5KIalpha is required for invadopodia formation and ECM degradation by human breast cancer cells. ..
- Xin X, Rabiner C, Mains R, Eipper B. Kalirin12 interacts with dynamin. BMC Neurosci. 2009;10:61 pubmed publisher..Kalirin12 may play a role in coordinating Rho GTPase-mediated changes in the actin cytoskeleton with dynamin-mediated changes in membrane trafficking. ..
- Matsushita Y, Ohya S, Suzuki Y, Itoda H, Kimura T, Yamamura H, et al. Inhibition of Kv1.3 potassium current by phosphoinositides and stromal-derived factor-1alpha in Jurkat T cells. Am J Physiol Cell Physiol. 2009;296:C1079-85 pubmed publisher..These novel inhibitory effects of phosphoinositides and SDF-1alpha on Kv1.3 current may have a significant function as a downregulation mechanism of Kv1.3 activity for the maintenance of T lymphocyte activation in immune responses. ..
- Lopez Izquierdo A, Ponce Balbuena D, Ferrer T, Rodríguez Menchaca A, Sanchez Chapula J. Thiopental inhibits function of different inward rectifying potassium channel isoforms by a similar mechanism. Eur J Pharmacol. 2010;638:33-41 pubmed publisher..The reduction of thiopental effects during PIP(2) treatment suggests that thiopental inhibition on Kir2.1 channels is related to channel-PIP(2) interaction...
- Lee S, Kim B, Jeong H, Min K, Liu T, Park J, et al. Enhanced phosphatidylinositol 4-phosphate 5-kinase alpha expression and PI(4,5)P2 production in LPS-stimulated microglia. Neurochem Int. 2010;57:600-7 pubmed publisher..These findings indicate that PIP5Kalpha upregulation and the subsequent rise in PI(4,5)P(2) in LPS-stimulated microglia may positively regulate microglial inflammatory responses. ..
- Koharudin L, Furey W, Liu H, Liu Y, Gronenborn A. The phox domain of sorting nexin 5 lacks phosphatidylinositol 3-phosphate (PtdIns(3)P) specificity and preferentially binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). J Biol Chem. 2009;284:23697-707 pubmed publisher..The distinct structural and PtdIns binding characteristics of SNX5-PX impart specific properties on SNX5, influencing retromer-mediated regulation of retrograde trafficking of transmembrane cargo receptors. ..