Thromb Haemost 2001; 86(01): 214-221
DOI: 10.1055/s-0037-1616219
Research Article
Schattauer GmbH

A Journey with Platelet P-Selectin: The Molecular Basis of Granule Secretion, Signalling and Cell Adhesion

Bruce Furie
1   Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
,
Barbara C. Furie
1   Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
,
Robert Flaumenhaft
1   Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
12 December 2017 (online)

Summary

P-selectin is a transmembrane protein that resides within the alpha granule membrane of unstimulated platelets. The “extracellular” domains face into the lumen of the granule and the cytoplasmic tail extends into the platelet cytoplasm. Upon platelet stimulation, P-selectin is phosphorylated and translocated to the plasma membrane via a secretory pathway. P-selectin in the plasma membrane surface is exposed and serves as a cell adhesion receptor to interact with other cell receptors, including PSGL-1 and GPIb. P-selectin upregulates tissue factor in monocytes and leads to leukocyte accumulation in areas of vascular injury associated with thrombosis and inflammation.

 
  • References

  • 1 Stenberg PE, McEver RP, Shuman MA, Jacques YV, Bainton DF. A platelet alpha granule membrane protein (GMP140) is expressed on the plasma membrane after activation. J Cell Biol 1985; 101: 880-6.
  • 2 Berman CL, Yeo EL, WencelDrake J, Furie BC, Ginsberg ML, Furie B. A platelet alpha granule membrane protein that is associated with the plasma membrane after activation: characterization and subcellular localization of platelet activation-dependent granule external membrane protein. J Clin Invest 1986; 78: 130-7.
  • 3 Bonfanti R, Furie BC, Furie B, Wagner DD. PADGEM is a component of Weibel-Palade bodies in endothelial cells. Blood 1989; 73: 1109-12.
  • 4 McEver RP, Beckstead JH, Moore KL, Marshall-Carlson L, Bainton DF. GMP140, a platelet alpha granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest 1989; 84: 929-9.
  • 5 Johnston GI, Cook RG, McEver RP. Cloning of GMP140, a granule membrane protein of platelets and endothelium: Sequence similarity to proteins involved in cell adhesion and inflammation. Cell 1989; 56: 1033-44.
  • 6 Crovello CS, Furie BC, and Furie B. Rapid phosphorylation and selective dephosphorylation of P-selectin accompanies platelet activation. J Biol Chem 1993; 268: 14590-3.
  • 7 Fujimoto T, McEver RP. The cytoplasmic domain of P-selectin is phosphorylated on serine and threonine residues. Blood 1993; 82: 1758-66.
  • 8 Crovello CS, Furie BC, Furie B. Histidine phosphorylation of P-selectin upon ligand-induced stimulation of human platelets: a novel pathway for cell activation-dependent signal transduction. Cell 1995; 82: 279-86.
  • 9 Mayadas TN, Johnson RC, Rayburn H, Hynes RO, Wagner DD. Leukocyte rolling and extravasation are severely compromised in P-selectin-deficient mice. Cell 1993; 74: 541-54.
  • 10 White JG, Clawson CC. The surface-connected canalicular system of blood platelets – a fenestrated membrane system. Am J Pathol 1980; 101: 353-64.
  • 11 Palade G. Intracellular aspects of the process of protein synthesis. Science 1975; 189: 347-58.
  • 12 Stenberg PE, Shuman MA, Levine SP, Bainton DF. Redistribution of alpha-granules and their contents in thrombin-stimulated platelets. J Cell Biol 1984; 98: 748-60.
  • 13 Ginsberg MH, Taylor L, Painter RG. The mechanism of thrombin-induced platelet factor 4 secretion. Blood 1980; 55: 661-8.
  • 14 White J. Platelet secretory process. Blood 1999; 93: 2422-5.
  • 15 Lefebvre P, White JG, Krumwiede MD, Cohen I. Role of actin in platelet function. Eur J Cell Biol 1993; 62: 194-204.
  • 16 White JG, Rao GH. Effects of a microtubule stabilizing agent on the response of platelets to vincristine. Blood 1982; 60: 474-83.
  • 17 White JG, Rao GH. Influence of a microtubule stabilizing agent on platelet structural physiology. Am J Pathol 1983; 112: 207-17.
  • 18 Wheeler-Jones CP, Saermark T, Kakkar VV, Authi KS. Mastoparan promotes exocytosis and increases intracellular cyclic AMP in human platelets. Evidence for the existence of a Gi-like mechanism of secretion. Biochem J 1992; 281: 465-72.
  • 19 Rubin R, Ponnappa BC, Thomas AP, Hoek JB. Ethanol stimulates shape change in human platelets by activation of phosphoinositide-specific phospholipase C. Arch Biochem Biophys 1988; 260: 480-92.
  • 20 Benistant C, Rubin R. Ethanol inhibits thrombin-induced secretion by human platelets at a site distinct from phospholipase C or protein kinase C. Biochem J 1990; 269: 489-97.
  • 21 Rubin R. Ethanol interferes with collagen-induced platelet activation by inhibition of arachidonic acid mobilization. Arch Biochem Biophys 1989; 270: 99-113.
  • 22 Marcu MG, Zhang L, Nau-Staudt K, Trifaro JM. Recombinant scinderin, an F-actin severing protein, increases calcium-induced release of serotonin from permeabilized platelets, an effect blocked by two scinderin-derived actin-binding peptides and phosphatidylinositol 4,5-bisphosphate. Blood 1996; 87: 20-4.
  • 23 Weimbs T, Low SH, Chapin SJ, Mostov KE, Bucher P, Hofmann K. A conserved domain is present in different families of vesicular fusion proteins: a new superfamily. Proc Natl Acad Sci USA 1997; 94: 3046-51.
  • 24 Sollner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, Rothman JE. SNAP receptors implicated in vesicle targeting and fusion. Nature 1993; 362: 318-24.
  • 25 Lin RC, Scheller RH. Structural organization of the synaptic exocytosis core complex. Neuron 1997; 19: 1087-94.
  • 26 Pevsner J, Hsu SC, Braun JE, Calakos N, Ting AE, Bennett MK, Scheller RH. Specificity and regulation of a synaptic vesicle docking complex. Neuron 1994; 13: 353-61.
  • 27 Sollner T, Bennett MK, Whiteheart SW, Scheller RH, Rothman JE. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell 1993; 75: 409-18.
  • 28 Flaumenhaft R, Croce K, Chen E, Furie B, Furie BC. Proteins of the exocytotic core complex mediate platelet alpha-granule secretion. Roles of vesicle-associated membrane protein, SNAP-23, and syntaxin 4. J Biol Chem 1999; 274: 2492-501.
  • 29 Lemons PP, Chen D, Bernstein AM, Bennett MK, Whiteheart SW. Regulated secretion in platelets: identification of elements of the platelet exocytosis machinery. Blood 1997; 90: 1490-500.
  • 30 Reed GL, Houng AK, Fitzgerald ML. Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion. Blood 1999; 93: 2617-26.
  • 31 Chen D, Bernstein AM, Lemons PP, Whiteheart SW. Molecular mechanisms of platelet exocytosis: role of SNAP-23 and syntaxin 2 in dense core granule release. Blood 2000; 95: 921-9.
  • 32 Bernstein AM, Whiteheart SW. Identification of a cellubrevin/vesicle associated membrane protein 3 homologue in human platelets. Blood 1999; 93: 571-9.
  • 33 Lemons PP, Chen D, Whiteheart SW. Molecular mechanisms of platelet exocytosis: requirements for alpha-granule release. Biochem Biophys Res Commun 2000; 267: 875-80.
  • 34 Polgar J, Reed GL. A critical role for N-ethylmaleimide-sensitive fusion protein (NSF) in platelet granule secretion. Blood 1999; 94: 1313-8.
  • 35 Sogaard M, Tani K, Ye RR, Geromanos S, Tempst P, Kirchhausen T, Rothman JE, Sollner T. A rab protein is required for the assembly of SNARE complexes in the docking of transport vesicles. Cell 1994; 78: 937-48.
  • 36 Brennwald P, Kearns B, Champion K, Keranen S, Bankaitis V, Novick P. Sec9 is a SNAP-25-like component of a yeast SNARE complex that may be the effector of Sec4 function in exocytosis. Cell 1994; 79: 245-58.
  • 37 Hay JC, Martin TF. Phosphatidylinositol transfer protein required for ATP-dependent priming of Ca(2+)-activated secretion. Nature 1993; 366: 572-5.
  • 38 Hay JC, Fisette PL, Jenkins GH, Fukami K, Takenawa T, Anderson RA, Martin TF. ATP-dependent inositide phosphorylation required for Ca(2+)-activated secretion. Nature 1995; 374: 173-7.
  • 39 Fensome A, Cunningham E, Prosser S, Tan SK, Swigart P, Thomas G, Hsuan J, Cockcroft S. ARF and PITP restore GTP gamma S-stimulated protein secretion from cytosol-depleted HL60 cells by promoting PIP2 synthesis. Curr Biol 1996; 6: 730-8.
  • 40 Way G, N Ol Cockcroft S. Activation of exocytosis by cross-linking of the IgE receptor is dependent on ADP-ribosylation factor 1-regulated phospholipase D in RBL-2H3 mast cells: evidence that the mechanism of activation is via regulation of phosphatidylinositol 4,5-bisphosphate synthesis. Biochem J 2000; 346: 63-70.
  • 41 Chung SH, Polgar J, Reed GL. Protein kinase C phosphorylation of syntaxin 4 in thrombin-activated human platelets. J Biol Chem 2000; 275: 25286-91.
  • 42 Croce K, Flaumenhaft R, Rivers M, Furie B, Furie BC, Herman IM, Potter DA. Inhibition of calpain blocks platelet secretion, aggregation, and spreading. J Biol Chem 1999; 274: 36321-7.
  • 43 Pinxteren JA, AJ OS, Larbi KY, Tatham PE, Gomperts BD. Thirty years of stimulus-secretion coupling: from Ca(2+) to GTP in the regulation of exocytosis. Biochimie 2000; 82: 385-93.
  • 44 Padfield PJ, Panesar N, Henderson P, Baldassare JJ. Differential effects of G-protein activators on 5-hydroxytryptamine and platelet-derived growth factor release from streptolysin-O-permeabilized human platelets. Biochem J 1996; 314: 123-8.
  • 45 Pfeffer S. Transport vesicle targeting: Tethers before SNAREs. Nature Cell Biology 1999; 1: 17-22.
  • 46 Horikawa HP, Saisu H, Ishizuka T, Sekine Y, Tsugita A, Odani S, Abe T. A complex of rab3A, SNAP-25, VAMP/synaptobrevin-2 and syntaxins in brain presynaptic terminals. FEBS Lett 1993; 330: 236-40.
  • 47 Lupashin VV, Waters MG. t-Snare activation through transient interaction with a rab-like guanosine triphosphatase. Science 1997; 276: 1255-8.
  • 48 Karniguian A, Zahraoui A, Tavitian A. Identification of small GTP-binding rab proteins in human platelets: thrombin-induced phosphorylation of rab3B, rab6, and rab8 proteins. Proc Natl Acad Sci USA 1993; 90: 7647-51.
  • 49 Shirakawa R, Yoshioka A, Horiuchi H, Nishioka H, Tabuchi A, Kita T. Small GTPase rab4 regulates Ca2+-induced alpha-granule secretion in platelets. J Biol Chem 2000; 275: 33844-9.
  • 50 Fitzgerald ML, Reed GL. Rab6 is phosphorylated in thrombin-activated platelets by a protein kinase C-dependent mechanism: effects on GTP/GDP binding and cellular distribution. Biochem J 1999; 342: 353-60.
  • 51 Rozenvayn N, Flaumenhaft R. Phosphatidylinositol (4,5)-bisphosphate mediates Ca2+-induced platelet α-granule secretion: Evidence for type II phosphatidylinositol 5-phosphate 4-kinase function. J Biol Chem. in press.
  • 52 Schiavo G, Gu QM, Prestwich GD, Sollner TH, Rothman JE. Calcium-dependent switching of the specificity of phosphoinositide binding to synaptotagmin. Proc Natl Acad Sci USA 1996; 93: 13327-32.
  • 53 Geppert M, Goda Y, Hammer RE, Li C, Rosahl TW, Stevens CF, Sudhof TC. Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse. Cell 1994; 79: 717-27.
  • 54 Schiavo G, Stenbeck G, Rothman JE, Sollner TH. Binding of the synaptic vesicle v-SNARE, synaptotagmin, to the plasma membrane t-SNARE, SNAP-25, can explain docked vesicles at neurotoxin-treated synapses. Proc Natl Acad Sci USA 1997; 94: 997-1001.
  • 55 Martin TF. Phosphoinositide lipids as signaling molecules: common themes for signal transduction, cytoskeletal regulation, and membrane trafficking. Annu Rev Cell Dev Biol 1998; 14: 231-64.
  • 56 Walker TR, Watson SP. Synergy between Ca2+ and protein kinase C is the major factor in determining the level of secretion from human platelets. Biochem J 1993; 289: 277-82.
  • 57 Sloan DC, Haslam RJ. Protein kinase C-dependent and Ca2+-dependent mechanisms of secretion from streptolysin O-permeabilized platelets: effects of leakage of cytosolic proteins. Biochem J 1997; 328: 13-21.
  • 58 Zimmerman UJ, Speicher DW, Fisher AB. Secretagogue-induced proteolysis of lung spectrin in alveolar epithelial type II cells. Biochim Biophys Acta 1992; 1137: 127-34.
  • 59 Zimmerman UJ, Malek SK, Liu L, Li HL. Proteolysis of synaptobrevin, syntaxin, and SNAP-25 in alveolar epithelial type II cells. IUBMB Life 1999; 48: 453-8.
  • 60 Larsen E, Celi A, Gilbert GE, Furie BC, Erban JK, Bonfanti R, Wagner DD, Furie B. PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 1989; 59: 305-12.
  • 61 Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 1991; 65: 859-73.
  • 62 Frenette PS, Mayadas TN, Rayburn H, Hynes RO, Wagner DD. Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell 1996; 84: 563-74.
  • 63 Larsen E, Palabrica T, Sajer S, Gilbert GE, Wagner DD, Furie BC, Furie B. PADGEM-dependent adhesion of platelets to monocytes and neutrophils is mediated by a lineage-specific carbohydrate, LNFIII (CD15). Cell 1990; 63: 467-74.
  • 64 Sako D, Chang XJ, Barone KM, Vachino G, White HM, Shaw G, Veldman GM, Bean KM, Ahern TJ, Furie B, Cumming DA, Larsen GR. Expression cloning of a functional glycoprotein ligand for P-selectin. Cell 1993; 75: 1179-86.
  • 65 Pouyani T, Seed B. PSGL-1 recognition of P-selectin is controlled by a tyrosine sulfation consensus at the PSGL-1 amino terminus. Cell 1995; 83: 333-43.
  • 66 Sako D, Comess KM, Barone KM, Camphausen RT, Cumming DA, Shaw GD. A sulfated peptide segment at the amino terminus of PSGL-1 is critical for P-selectin binding. Cell 1995; 83: 323-31.
  • 67 Wilkins PP, Moore KL, McEver RP, Cummings RD. Tyrosine sulfation of P-selectin glycoprotein ligand-1 is required for high affinity binding to P-selectin. J Biol Chem 1995; 270: 22677-80.
  • 68 Croce K, Freedman SJ, Furie BC, Furie B. Interaction of soluble P-selectin and soluble PSGL-1: Equilibrium binding analysis. Biochemistry 1998; 37: 16472-80.
  • 69 Somers WS, Tang J, Shaw GD, Camphausen RT. Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1. Cell 2000; 103: 467-79.
  • 70 Yang J, Hirata T, Croce K, Merrill-Skoloff G, Tchernychev B, Williams E, Flaumenhaft R, Furie BC, Furie B. Targeted gene disruption demonstrates that PSGL-1 is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration. J Exp Med 1999; 190: 1769-82.
  • 71 Hirata T, Merrill-Skoloff G, Aab M, Yang J, Furie BC, Furie B. P-selectin glycoprotein ligand-1 (PSGL-1) is a physiological ligand for E-selectin in mediating T helper1 lymphocyte migration. J Exp Med 2000; 192: 1669-76.
  • 72 Frenette PS, Johnson RC, Hynes RO, Wagner DD. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci USA 1995; 92: 7450-4.
  • 73 Frenette PS, Denis CV, Weiss L, Jurk K, Subbarao S, Kehrel B, Hartwig JH, Vestweber D, Wagner DD. P-Selectin glycoprotein ligand 1 (PSGL1) is expressed on platelets and can mediate platelet endothelial interactions in vivo. J Exp Med 2000; 191: 1413-22.
  • 74 Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, Lopez JA. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med 1999; 190: 803-14.
  • 75 Gross PL, Merrill-Skoloff G, Aab M, Croce K, Ware J, Ruggeri ZM, Furie BC, Furie B. Glycoprotein Ib and PSGL-1 serve as platelet ligands for platelet-endothelial cell interaction during platelet rolling on stimulated postcapillary venules in vivo. Blood 2000; 96: 812a (abstr).
  • 76 Celi A, Pellegrini G, Lorenzet R, De Blasi A, Ready N, Furie BC, Furie B. P-selectin induces the expression of tissue factor on monocytes. Proc Nat Acad Sci 1994; 91: 8767-71.
  • 77 Pellegrini G, Malandra R, Celi A, Furie BC, Furie B, Lorenzet R. 12-Hydroxyeicosatetraenoic acid up-regulates P-selectin-induced tissue factor activity on monocytes. FEBS Lett 1999; 441: 463-6.
  • 78 Elstad MR, La Pine TR, Cowley FS, McEver RP, McIntyre TM, Prescott SM, Zimmerman GA. P-selectin regulates platelet activating factor synthesis and phagocytosis by monocytes. J Immunol 1995; 155: 2109-22.
  • 79 Weyrich AS, McIntyre TM, McEver RP, Prescott SM, Zimmerman GA. Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B translocation. J Clin Invest 1995; 95: 2297-303.
  • 80 Weyrich AS, Elstad MR, McEver RP, McIntyre TM, Moore KL, Morrissey JH, Prescott SM, Zimmerman GA. Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 1996; 97: 1525-34.
  • 81 Hidari K, Weyrich A, Zimmerman G, McEver R. Engagement of P-selectin glycoprotein ligand-1 enhances tyrosine phosphorylation and activates mitogen-activated protein kinases in human neutrophils. J Biol Chem 1997; 272: 28750-6.
  • 82 Haller H, Kunzendorf U, Sacherer K, Lindschau C, Walz G, Distler A, Luft FC. T cell adhesion to P-selectin induces tyrosine phosphorylation of pp125 focal adhesion kinase and other substrates. J Immunol 1997; 158: 1061-7.
  • 83 Piccardoni P, Sideri R, Piccoli A, Cerletti C, Gaetano G, Manarini S, Evangelista V. Platelet/PMN adhesion: Role of src kinases in the P-selectin induced Mac-1 adhesive function. Blood 2000; 96: 608a (abstr).
  • 84 Palabrica T, Lobb R, Furie BC, Aronovitz M, Benjamin C, Hsu YM, Sajer SA, Furie B. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature 1992; 359: 848-51.
  • 85 Schmidtke DW, Diamond SL. Direct observation of membrane tethers formed during neutrophil attachment to platelets or P-selectin under physiological flow. J Cell Biol 2000; 149: 719-30.
  • 86 Giesen PL, Rauch U, Bohrmann B, Kling D, Roque M, Fallon JT, Badimon JJ, Himber J, Riederer MA, Nemerson Y. Blood-borne tissue factor: Another view of thrombosis. Proc Nat Acad Sci USA 1999; 96: 2311-5.
  • 87 Rauch U, Bonderman D, Bohrmann B, Badimon JJ, Himber J, Riederer MA, Nemerson Y. Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor. Blood 2000; 96: 170-5.
  • 88 Subramaniam M, Frenette PS, Saffaripour S, Johnson RC, Hynes RO, Wagner DD. Defects in hemostasis in P-selectin-deficient mice. Blood 1996; 87: 1238-42.
  • 89 Ruggeri ZM, Subramanian M, Dent JA, Wagner DD, Saldivar E. P-Selectin and the three dimensional structure of platelet thrombi. Blood 2000; 96: 812a (abstr).