• 1
    Stegner D, Nieswandt B. Platelet receptor signaling in thrombus formation. J Mol Med 2011; 89: 10921.
  • 2
    Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002; 8: 122734.
  • 3
    Bhatt DL, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov 2003; 2: 1528.
  • 4
    Stoll G, Kleinschnitz C, Nieswandt B. Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood 2008; 112: 355562.
  • 5
    Nieswandt B, Watson SP. Platelet–collagen interaction: is GPVI the central receptor? Blood 2003; 102: 44961.
  • 6
    Offermanns S. Activation of platelet function through G protein-coupled receptors. Circ Res 2006; 99: 1293304.
  • 7
    Shattil SJ, Kim C, Ginsberg MH. The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol 2010; 11: 288300.
  • 8
    Blair P, Flaumenhaft R. Platelet alpha-granules: basic biology and clinical correlates. Blood Rev 2009; 23: 17789.
  • 9
    McDermott M, Wakelam MJ, Morris AJ. Phospholipase D. Biochem Cell Biol 2004; 82: 22553.
  • 10
    Morris AJ, Frohman MA, Engebrecht J. Measurement of phospholipase D activity. Anal Biochem 1997; 252: 19.
  • 11
    Hammond SM, Altshuller YM, Sung TC, Rudge SA, Rose K, Engebrecht J, Morris AJ, Frohman MA. Human ADP-ribosylation factor-activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family. J Biol Chem 1995; 270: 296403.
  • 12
    Kodaki T, Yamashita S. Cloning, expression, and characterization of a novel phospholipase D complementary DNA from rat brain. J Biol Chem 1997; 272: 1140813.
  • 13
    Cazzolli R, Shemon AN, Fang MQ, Hughes WE. Phospholipid signalling through phospholipase D and phosphatidic acid. IUBMB Life 2006; 58: 45761.
  • 14
    Oude Weernink PA, Lopez de Jesus M, Schmidt M. Phospholipase D signaling: orchestration by PIP2 and small GTPases. Naunyn Schmiedebergs Arch Pharmacol 2007; 374: 399411.
  • 15
    Rudge SA, Wakelam MJ. Inter-regulatory dynamics of phospholipase D and the actin cytoskeleton. Biochim Biophys Acta 2009; 1791: 85661.
  • 16
    Sung TC, Zhang Y, Morris AJ, Frohman MA. Structural analysis of human phospholipase D1. J Biol Chem 1999; 274: 365966.
  • 17
    Gomez-Cambronero J. The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2, Sos, WASp and Rac2 (and a surprise discovery: PLD2 is a GEF). Cell Signal 2011; 23: 188595.
  • 18
    Kim JH, Kim Y, Lee SD, Lopez I, Arnold RS, Lambeth JD, Suh PG, Ryu SH. Selective activation of phospholipase D2 by unsaturated fatty acid. FEBS Lett 1999; 454: 426.
  • 19
    Martinson EA, Scheible S, Greinacher A, Presek P. Platelet phospholipase D is activated by protein kinase C via an integrin alpha IIb beta 3-independent mechanism. Biochem J 1995; 310: 6238.
  • 20
    Vorland M, Holmsen H. Phospholipase D in human platelets: presence of isoenzymes and participation of autocrine stimulation during thrombin activation. Platelets 2008; 19: 21124.
  • 21
    Coorssen JR, Haslam RJ. GTP gamma S and phorbol ester act synergistically to stimulate both Ca(2+)-independent secretion and phospholipase D activity in permeabilized human platelets. Inhibition by BAPTA and analogues. FEBS Lett 1993; 316: 1704.
  • 22
    Dall’armi C, Hurtado-Lorenzo A, Tian H, Morel E, Nezu A, Chan RB, Yu WH, Robinson KS, Yeku O, Small SA, Duff K, Frohman MA, Wenk MR, Yamamoto A, Di Paolo G. The phospholipase D1 pathway modulates macroautophagy. Nat Commun 2010; 1: 142.
  • 23
    Elvers M, Stegner D, Hagedorn I, Kleinschnitz C, Braun A, Kuijpers ME, Boesl M, Chen Q, Heemskerk JW, Stoll G, Frohman MA, Nieswandt B. Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1. Sci Signal 2010; 3: ra1.
  • 24
    Oliveira TG, Chan RB, Tian H, Laredo M, Shui G, Staniszewski A, Zhang H, Wang L, Kim TW, Duff KE, Wenk MR, Arancio O, Di Paolo G. Phospholipase d2 ablation ameliorates Alzheimer’s disease-linked synaptic dysfunction and cognitive deficits. J Neurosci 2010; 30: 1641928.
  • 25
    Su W, Yeku O, Olepu S, Genna A, Park JS, Ren H, Du G, Gelb MH, Morris AJ, Frohman MA. 5-Fluoro-2-indolyl des-chlorohalopemide (FIPI), a phospholipase D pharmacological inhibitor that alters cell spreading and inhibits chemotaxis. Mol Pharmacol 2009; 75: 43746.
  • 26
    Elvers M, Grenegard M, Khoshjabinzadeh H, Munzer P, Borst O, Tian H, Di Paolo G, Lang F, Gawaz M, Lindahl TL, Falker K. A novel role for phospholipase D as an endogenous negative regulator of platelet sensitivity. Cell Signal 2012; 24: 174352.
  • 27
    Knight CG, Morton LF, Onley DJ, Peachey AR, Ichinohe T, Okuma M, Farndale RW, Barnes MJ. Collagen–platelet interaction: Gly-Pro-Hyp is uniquely specific for platelet Gp VI and mediates platelet activation by collagen. Cardiovasc Res 1999; 41: 4507.
  • 28
    Pleines I, Eckly A, Elvers M, Hagedorn I, Eliautou S, Bender M, Wu X, Lanza F, Gachet C, Brakebusch C, Nieswandt B. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. Blood 2010; 115: 336473.
  • 29
    Nieswandt B, Brakebusch C, Bergmeier W, Schulte V, Bouvard D, Mokhtari-Nejad R, Lindhout T, Heemskerk JW, Zirngibl H, Fassler R. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen. EMBO J 2001; 20: 212030.
  • 30
    Grosse J, Braun A, Varga-Szabo D, Beyersdorf N, Schneider B, Zeitlmann L, Hanke P, Schropp P, Muhlstedt S, Zorn C, Huber M, Schmittwolf C, Jagla W, Yu P, Kerkau T, Schulze H, Nehls M, Nieswandt B. An EF hand mutation in Stim1 causes premature platelet activation and bleeding in mice. J Clin Invest 2007; 117: 354050.
  • 31
    Dirnagl U. Bench to bedside: the quest for quality in experimental stroke research. J Cereb Blood Flow Metab 2006; 26: 146578.
  • 32
    Kleinschnitz C, Pozgajova M, Pham M, Bendszus M, Nieswandt B, Stoll G. Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding. Circulation 2007; 115: 232330.
  • 33
    Colley WC, Sung TC, Roll R, Jenco J, Hammond SM, Altshuller Y, Bar-Sagi D, Morris AJ, Frohman MA. Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization. Curr Biol 1997; 7: 191201.
  • 34
    Choudhri TF, Hoh BL, Zerwes HG, Prestigiacomo CJ, Kim SC, Connolly ES Jr, Kottirsch G, Pinsky DJ. Reduced microvascular thrombosis and improved outcome in acute murine stroke by inhibiting GP IIb/IIIa receptor-mediated platelet aggregation. J Clin Invest 1998; 102: 130110.
  • 35
    Kauffenstein G, Bergmeier W, Eckly A, Ohlmann P, Leon C, Cazenave JP, Nieswandt B, Gachet C. The P2Y(12) receptor induces platelet aggregation through weak activation of the alpha(IIb)beta(3) integrin – a phosphoinositide 3-kinase-dependent mechanism. FEBS Lett 2001; 505: 28190.
  • 36
    Nieswandt B, Schulte V, Zywietz A, Gratacap MP, Offermanns S. Costimulation of Gi- and G12/G13-mediated signaling pathways induces integrin alpha IIbbeta 3 activation in platelets. J Biol Chem 2002; 277: 394938.
  • 37
    Wiczer BM, Thomas G. Phospholipase D and mTORC1: nutrients are what bring them together. Sci Signal 2012; 5: pe13.
  • 38
    Snell DC, Schulte V, Jarvis GE, Arase K, Sakurai D, Saito T, Watson SP, Nieswandt B. Differential effects of reduced glycoprotein VI levels on activation of murine platelets by glycoprotein VI ligands. Biochem J 2002; 368: 293300.
  • 39
    Cheli Y, Jensen D, Marchese P, Habart D, Wiltshire T, Cooke M, Fernandez JA, Ware J, Ruggeri ZM, Kunicki TJ. The Modifier of hemostasis (Mh) locus on chromosome 4 controls in vivo hemostasis of Gp6−/− mice. Blood 2008; 111: 126673.
  • 40
    Harper MT, Poole AW. Diverse functions of protein kinase C isoforms in platelet activation and thrombus formation. J Thromb Haemost 2010; 8: 45462.
  • 41
    Jang JH, Lee CS, Hwang D, Ryu SH. Understanding of the roles of phospholipase D and phosphatidic acid through their binding partners. Prog Lipid Res 2012; 51: 7181.
  • 42
    Konopatskaya O, Gilio K, Harper MT, Zhao Y, Cosemans JM, Karim ZA, Whiteheart SW, Molkentin JD, Verkade P, Watson SP, Heemskerk JW, Poole AW. PKCalpha regulates platelet granule secretion and thrombus formation in mice. J Clin Invest 2009; 119: 399407.
  • 43
    Ren Q, Barber HK, Crawford GL, Karim ZA, Zhao C, Choi W, Wang CC, Hong W, Whiteheart SW. Endobrevin/VAMP-8 is the primary v-SNARE for the platelet release reaction. Mol Biol Cell 2007; 18: 2433.
  • 44
    Vicogne J, Vollenweider D, Smith JR, Huang P, Frohman MA, Pessin JE. Asymmetric phospholipid distribution drives in vitro reconstituted SNARE-dependent membrane fusion. Proc Natl Acad Sci USA 2006; 103: 147616.