Ca2+ waves coordinate purinergic receptor–evoked integrin activation and polarizationBye, A. P. ORCID: https://orcid.org/0000-0002-2061-2253, Gibbins, J. M. ORCID: https://orcid.org/0000-0002-0372-5352 and Mahaut-Smith, M. P. (2020) Ca2+ waves coordinate purinergic receptor–evoked integrin activation and polarization. Science Signaling, 13 (615). eaav7354. ISSN 1937-9145
It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing. To link to this item DOI: 10.1126/scisignal.aav7354 Abstract/SummaryThe integrin GPIIb/IIIa is highly abundant on the surface of platelets and can be activated by intracellular Ca2+ signaling in an “inside-out” manner to bind to the adhesive ligand fibrinogen. Bye et al. imaged intracellular Ca2+ signaling and fibrinogen binding events in primary rat megakaryocytes activated through the ADP-stimulated receptors P2Y1 and P2Y12. The authors found that signaling by both receptors was required for full integrin activation, which depended on P2Y1-stimulated Ca2+ signaling and P2Y12-stimulated activation of the kinase PI3K. In addition, fibrinogen binding became polarized in these cells in a manner dependent on the direction of ADP-stimulated Ca2+ waves.
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• B. Nieswandt, D. Varga-Szabo, M. Elvers, Integrins in platelet activation. Journal of thrombosis and haemostasis : JTH 7 Suppl 1, 206-209 (2009); published online EpubJul (10.1111/j.1538-7836.2009.03370.x).
• C. Kim, F. Ye, M. H. Ginsberg, Regulation of integrin activation. Annu Rev Cell Dev Biol 27, 321-345 (2011)10.1146/annurev-cellbio-100109-104104).
• L. Stefanini, R. C. Roden, W. Bergmeier, CalDAG-GEFI is at the nexus of calcium-dependent platelet activation. Blood 114, 2506-2514 (2009); published online EpubSep 17 (10.1182/blood-2009-04-218768).
• K. Eto, R. Murphy, S. W. Kerrigan, A. Bertoni, H. Stuhlmann, T. Nakano, A. D. Leavitt, S. J. Shattil, Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling. Proc Natl Acad Sci U S A 99, 12819-12824 (2002); published online EpubOct 1 (10.1073/pnas.202380099).
• L. Stefanini, D. S. Paul, R. F. Robledo, E. R. Chan, T. M. Getz, R. A. Campbell, D. O. Kechele, C. Casari, R. Piatt, K. M. Caron, N. Mackman, A. S. Weyrich, M. C. Parrott, Y. Boulaftali, M. D. Adams, L. L. Peters, W. Bergmeier, RASA3 is a critical inhibitor of RAP1-dependent platelet activation. J Clin Invest 125, 1419-1432 (2015); published online EpubApr (10.1172/JCI77993).
• L. Stefanini, W. Bergmeier, RAP1-GTPase signaling and platelet function. J Mol Med (Berl) 94, 13-19 (2016); published online EpubJan (10.1007/s00109-015-1346-3).
• A. M. Battram, T. N. Durrant, E. O. Agbani, K. J. Heesom, D. S. Paul, R. Piatt, A. W. Poole, P. J. Cullen, W. Bergmeier, S. F. Moore, I. Hers, The Phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) Binder Rasa3 Regulates Phosphoinositide 3-kinase (PI3K)-dependent Integrin alphaIIbbeta3 Outside-in Signaling. J Biol Chem 292, 1691-1704 (2017); published online EpubFeb 3 (10.1074/jbc.M116.746867).
• F. Lagarrigue, C. Kim, M. H. Ginsberg, The Rap1-RIAM-talin axis of integrin activation and blood cell function. Blood 128, 479-487 (2016); published online EpubJul 28 (10.1182/blood-2015-12-638700).
• G. Dupont, L. Combettes, G. S. Bird, J. W. Putney, Calcium oscillations. Cold Spring Harbor perspectives in biology 3, (2011); published online EpubMar (10.1101/cshperspect.a004226).
• A. B. Parekh, Decoding cytosolic Ca2+ oscillations. Trends in biochemical sciences 36, 78-87 (2011); published online EpubFeb (10.1016/j.tibs.2010.07.013).
• R. E. Dolmetsch, K. Xu, R. S. Lewis, Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392, 933-936 (1998); published online EpubApr 30 (10.1038/31960).
• S. Wray, T. Burdyga, Sarcoplasmic reticulum function in smooth muscle. Physiological reviews 90, 113-178 (2010); published online EpubJan (10.1152/physrev.00018.2008).
• K. Machaca, Ca2+ signaling differentiation during oocyte maturation. Journal of cellular physiology 213, 331-340 (2007); published online EpubNov (10.1002/jcp.21194).
• A. H. Cornell-Bell, S. M. Finkbeiner, M. S. Cooper, S. J. Smith, Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247, 470-473 (1990); published online EpubJan 26 (
• M. J. Berridge, Inositol trisphosphate and calcium signalling mechanisms. Biochimica et biophysica acta 1793, 933-940 (2009); published online EpubJun (10.1016/j.bbamcr.2008.10.005).
• L. T. Izu, Y. Xie, D. Sato, T. Banyasz, Y. Chen-Izu, Ca(2)(+) waves in the heart. Journal of molecular and cellular cardiology 58, 118-124 (2013); published online EpubMay (10.1016/j.yjmcc.2012.11.014).
• J. W. Heemskerk, J. Hoyland, W. T. Mason, S. O. Sage, Spiking in cytosolic calcium concentration in single fibrinogen-bound fura-2-loaded human platelets. Biochem J 283 ( Pt 2), 379-383 (1992); published online EpubApr 15 (
• M. Mazzucato, M. R. Cozzi, M. Battiston, M. Jandrot-Perrus, M. Mongiat, P. Marchese, T. J. Kunicki, Z. M. Ruggeri, L. De Marco, Distinct spatio-temporal Ca2+ signaling elicited by integrin alpha2beta1 and glycoprotein VI under flow. Blood 114, 2793-2801 (2009); published online EpubSep 24 (10.1182/blood-2008-12-193490).
• S. I. Obydennyy, A. N. Sveshnikova, F. I. Ataullakhanov, M. A. Panteleev, Dynamics of calcium spiking, mitochondrial collapse and phosphatidylserine exposure in platelet subpopulations during activation. Journal of thrombosis and haemostasis : JTH, (2016); published online EpubJun 25 (10.1111/jth.13395).
• N. N. Topalov, Y. N. Kotova, S. A. Vasil'ev, M. A. Panteleev, Identification of signal transduction pathways involved in the formation of platelet subpopulations upon activation. British journal of haematology 157, 105-115 (2012); published online EpubApr (10.1111/j.1365-2141.2011.09021.x).
• F. Ye, C. Kim, M. H. Ginsberg, Reconstruction of integrin activation. Blood 119, 26-33 (2012); published online EpubJan 5 (10.1182/blood-2011-04-292128).
• S. Tertyshnikova, A. Fein, [Ca2+]i oscillations and [Ca2+]i waves in rat megakaryocytes. Cell calcium 21, 331-344 (1997); published online EpubMay (
• D. Thomas, M. J. Mason, M. P. Mahaut-Smith, Depolarisation-evoked Ca2+ waves in the non-excitable rat megakaryocyte. The Journal of physiology 537, 371-378 (2001); published online EpubDec 1 (
• S. J. Shattil, A. D. Leavitt, All in the family: primary megakaryocytes for studies of platelet alphaIIbbeta3 signaling. Thrombosis and haemostasis 86, 259-265 (2001); published online EpubJul (
• G. Tolhurst, C. Vial, C. Leon, C. Gachet, R. J. Evans, M. P. Mahaut-Smith, Interplay between P2Y(1), P2Y(12), and P2X(1) receptors in the activation of megakaryocyte cation influx currents by ADP: evidence that the primary megakaryocyte represents a fully functional model of platelet P2 receptor signaling. Blood 106, 1644-1651 (2005); published online EpubSep 1 (10.1182/blood-2005-02-0725).
• S. Jones, R. J. Evans, M. P. Mahaut-Smith, Extracellular Ca(2+) modulates ADP-evoked aggregation through altered agonist degradation: implications for conditions used to study P2Y receptor activation. British journal of haematology 153, 83-91 (2011); published online EpubApr (10.1111/j.1365-2141.2010.08499.x).
• B. Z. Paul, J. L. Daniel, S. P. Kunapuli, Platelet shape change is mediated by both calcium-dependent and -independent signaling pathways. Role of p160 Rho-associated coiled-coil-containing protein kinase in platelet shape change. J Biol Chem 274, 28293-28300 (1999); published online EpubOct 1 (
• J. R. Crittenden, W. Bergmeier, Y. Zhang, C. L. Piffath, Y. Liang, D. D. Wagner, D. E. Housman, A. M. Graybiel, CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation. Nature medicine 10, 982-986 (2004); published online EpubSep (10.1038/nm1098).
• G. Hollopeter, H. M. Jantzen, D. Vincent, G. Li, L. England, V. Ramakrishnan, R. B. Yang, P. Nurden, A. Nurden, D. Julius, P. B. Conley, Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 409, 202-207 (2001); published online EpubJan 11 (10.1038/35051599).
• J. M. Cosemans, I. C. Munnix, R. Wetzker, R. Heller, S. P. Jackson, J. W. Heemskerk, Continuous signaling via PI3K isoforms beta and gamma is required for platelet ADP receptor function in dynamic thrombus stabilization. Blood 108, 3045-3052 (2006); published online EpubNov 1 (10.1182/blood-2006-03-006338).
• J. E. Fabre, M. Nguyen, A. Latour, J. A. Keifer, L. P. Audoly, T. M. Coffman, B. H. Koller, Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice. Nature medicine 5, 1199-1202 (1999); published online EpubOct (10.1038/13522).
• C. J. Foster, D. M. Prosser, J. M. Agans, Y. Zhai, M. D. Smith, J. E. Lachowicz, F. L. Zhang, E. Gustafson, F. J. Monsma, Jr., M. T. Wiekowski, S. J. Abbondanzo, D. N. Cook, M. L. Bayne, S. A. Lira, M. S. Chintala, Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs. The Journal of clinical investigation 107, 1591-1598 (2001); published online EpubJun (10.1172/JCI12242).
• B. Hechler, A. Eckly, P. Ohlmann, J. P. Cazenave, C. Gachet, The P2Y1 receptor, necessary but not sufficient to support full ADP-induced platelet aggregation, is not the target of the drug clopidogrel. British journal of haematology 103, 858-866 (1998); published online EpubDec (
• J. Jin, S. P. Kunapuli, Coactivation of two different G protein-coupled receptors is essential for ADP-induced platelet aggregation. Proceedings of the National Academy of Sciences of the United States of America 95, 8070-8074 (1998); published online EpubJul 7 (
• C. Leon, B. Hechler, M. Freund, A. Eckly, C. Vial, P. Ohlmann, A. Dierich, M. LeMeur, J. P. Cazenave, C. Gachet, Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y(1) receptor-null mice. The Journal of clinical investigation 104, 1731-1737 (1999); published online EpubDec (10.1172/JCI8399).
• J. Jin, J. L. Daniel, S. P. Kunapuli, Molecular basis for ADP-induced platelet activation. II. The P2Y1 receptor mediates ADP-induced intracellular calcium mobilization and shape change in platelets. J Biol Chem 273, 2030-2034 (1998); published online EpubJan 23 (
• T. J. Hallam, T. J. Rink, Responses to adenosine diphosphate in human platelets loaded with the fluorescent calcium indicator quin2. The Journal of physiology 368, 131-146 (1985); published online EpubNov (
• S. J. Mundell, M. L. Jones, A. R. Hardy, J. F. Barton, S. M. Beaucourt, P. B. Conley, A. W. Poole, Distinct roles for protein kinase C isoforms in regulating platelet purinergic receptor function. Molecular pharmacology 70, 1132-1142 (2006); published online EpubSep (10.1124/mol.106.023549).
• A. R. Hardy, P. B. Conley, J. Luo, J. L. Benovic, A. W. Poole, S. J. Mundell, P2Y1 and P2Y12 receptors for ADP desensitize by distinct kinase-dependent mechanisms. Blood 105, 3552-3560 (2005); published online EpubMay 1 (10.1182/blood-2004-07-2893).
• S. O. Sage, E. H. Yamoah, J. W. Heemskerk, The roles of P(2X1)and P(2T AC)receptors in ADP-evoked calcium signalling in human platelets. Cell calcium 28, 119-126 (2000); published online EpubAug (10.1054/ceca.2000.0139).
• A. R. Hardy, M. L. Jones, S. J. Mundell, A. W. Poole, Reciprocal cross-talk between P2Y1 and P2Y12 receptors at the level of calcium signaling in human platelets. Blood 104, 1745-1752 (2004); published online EpubSep 15 (10.1182/blood-2004-02-0534).
• S. M. Schoenwaelder, A. Ono, S. Sturgeon, S. M. Chan, P. Mangin, M. J. Maxwell, S. Turnbull, M. Mulchandani, K. Anderson, G. Kauffenstein, G. W. Rewcastle, J. Kendall, C. Gachet, H. H. Salem, S. P. Jackson, Identification of a unique co-operative phosphoinositide 3-kinase signaling mechanism regulating integrin alpha IIb beta 3 adhesive function in platelets. J Biol Chem 282, 28648-28658 (2007); published online EpubSep 28 (10.1074/jbc.M704358200).
• D. Woulfe, H. Jiang, R. Mortensen, J. Yang, L. F. Brass, Activation of Rap1B by G(i) family members in platelets. J Biol Chem 277, 23382-23390 (2002); published online EpubJun 28 (10.1074/jbc.M202212200).
• G. F. Guidetti, I. Canobbio, M. Torti, PI3K/Akt in platelet integrin signaling and implications in thrombosis. Adv Biol Regul 59, 36-52 (2015); published online EpubSep (10.1016/j.jbior.2015.06.001).
• G. Kauffenstein, W. Bergmeier, A. Eckly, P. Ohlmann, C. Leon, J. P. Cazenave, B. Nieswandt, C. Gachet, The P2Y(12) receptor induces platelet aggregation through weak activation of the alpha(IIb)beta(3) integrin--a phosphoinositide 3-kinase-dependent mechanism. FEBS letters 505, 281-290 (2001); published online EpubSep 14 (
• J. L. Joyal, D. J. Burks, S. Pons, W. F. Matter, C. J. Vlahos, M. F. White, D. B. Sacks, Calmodulin activates phosphatidylinositol 3-kinase. J Biol Chem 272, 28183-28186 (1997); published online EpubNov 7 (
• W. Chen, I. Thielmann, S. Gupta, H. Subramanian, D. Stegner, R. van Kruchten, A. Dietrich, S. Gambaryan, J. W. Heemskerk, H. M. Hermanns, B. Nieswandt, A. Braun, Orai1-induced store-operated Ca(2+) entry enhances phospholipase activity and modulates canonical transient receptor potential channel 6 function in murine platelets. Journal of thrombosis and haemostasis : JTH 12, 528-539 (2014); published online EpubApr (10.1111/jth.12525).
• A. K. Rao, M. A. Kowalska, J. Disa, Impaired cytoplasmic ionized calcium mobilization in inherited platelet secretion defects. Blood 74, 664-672 (1989); published online EpubAug 1 (
• X. Yang, L. Sun, S. Ghosh, A. K. Rao, Human platelet signaling defect characterized by impaired production of inositol-1,4,5-triphosphate and phosphatidic acid and diminished Pleckstrin phosphorylation: evidence for defective phospholipase C activation. Blood 88, 1676-1683 (1996); published online EpubSep 1 (
• S. B. Lee, A. K. Rao, K. H. Lee, X. Yang, Y. S. Bae, S. G. Rhee, Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function. Blood 88, 1684-1691 (1996); published online EpubSep 1 (
• R. C. Liddington, M. H. Ginsberg, Integrin activation takes shape. J Cell Biol 158, 833-839 (2002); published online EpubSep 2 (10.1083/jcb.200206011).
• D. R. Critchley, Cytoskeletal proteins talin and vinculin in integrin-mediated adhesion. Biochem Soc Trans 32, 831-836 (2004); published online EpubNov (10.1042/BST0320831).
• S. Miyamoto, S. K. Akiyama, K. M. Yamada, Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function. Science 267, 883-885 (1995); published online EpubFeb 10 (
• J. Zhu, C. V. Carman, M. Kim, M. Shimaoka, T. A. Springer, B. H. Luo, Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling. Blood 110, 2475-2483 (2007); published online EpubOct 1 (10.1182/blood-2007-03-080077).
• C. Cluzel, F. Saltel, J. Lussi, F. Paulhe, B. A. Imhof, B. Wehrle-Haller, The mechanisms and dynamics of (alpha)v(beta)3 integrin clustering in living cells. J Cell Biol 171, 383-392 (2005); published online EpubOct 24 (10.1083/jcb.200503017).
• W. Li, J. Llopis, M. Whitney, G. Zlokarnik, R. Y. Tsien, Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression. Nature 392, 936-941 (1998); published online EpubApr 30 (10.1038/31965).
• N. Pugh, B. D. Maddox, D. Bihan, K. A. Taylor, M. P. Mahaut-Smith, R. W. Farndale, Differential integrin activity mediated by platelet collagen receptor engagement under flow conditions. Thrombosis and haemostasis 117, 1588-1600 (2017); published online EpubJul 26 (10.1160/TH16-12-0906).
• W. S. Nesbitt, S. Kulkarni, S. Giuliano, I. Goncalves, S. M. Dopheide, C. L. Yap, I. S. Harper, H. H. Salem, S. P. Jackson, Distinct glycoprotein Ib/V/IX and integrin alpha IIbbeta 3-dependent calcium signals cooperatively regulate platelet adhesion under flow. J Biol Chem 277, 2965-2972 (2002); published online EpubJan 25 (10.1074/jbc.M110070200).
• J. W. Heemskerk, P. Vis, M. A. Feijge, J. Hoyland, W. T. Mason, S. O. Sage, Roles of phospholipase C and Ca(2+)-ATPase in calcium responses of single, fibrinogen-bound platelets. J Biol Chem 268, 356-363 (1993); published online EpubJan 5 (
• C. Uneyama, H. Uneyama, N. Akaike, Cytoplasmic Ca2+ oscillation in rat megakaryocytes evoked by a novel type of purinoceptor. The Journal of physiology 470, 731-749 (1993); published online EpubOct (
• M. Iino, Spatiotemporal dynamics of Ca2+ signaling and its physiological roles. Proc Jpn Acad Ser B Phys Biol Sci 86, 244-256 (2010).
• C. D. Lawson, K. Burridge, The on-off relationship of Rho and Rac during integrin-mediated adhesion and cell migration. Small GTPases 5, e27958 (2014)10.4161/sgtp.27958).
• F. Moheimani, D. E. Jackson, P2Y12 receptor: platelet thrombus formation and medical interventions. Int J Hematol 96, 572-587 (2012); published online EpubNov (10.1007/s12185-012-1188-5).
• G. Berger, R. Quarck, D. Tenza, S. Levy-Toledano, J. de Gunzburg, E. M. Cramer, Ultrastructural localization of the small GTP-binding protein Rap1 in human platelets and megakaryocytes. British journal of haematology 88, 372-382 (1994); published online EpubOct (
• K. Nagata, Y. Nozawa, A low M(r) GTP-binding protein, Rap1, in human platelets: localization, translocation and phosphorylation by cyclic AMP-dependent protein kinase. British journal of haematology 90, 180-186 (1995); published online EpubMay (
• M. J. Caloca, J. L. Zugaza, M. Vicente-Manzanares, F. Sanchez-Madrid, X. R. Bustelo, F-actin-dependent translocation of the Rap1 GDP/GTP exchange factor RasGRP2. J Biol Chem 279, 20435-20446 (2004); published online EpubMay 7 (10.1074/jbc.M313013200).
• J. Clyde-Smith, G. Silins, M. Gartside, S. Grimmond, M. Etheridge, A. Apolloni, N. Hayward, J. F. Hancock, Characterization of RasGRP2, a plasma membrane-targeted, dual specificity Ras/Rap exchange factor. J Biol Chem 275, 32260-32267 (2000); published online EpubOct 13 (10.1074/jbc.M006087200).
• M. C. Beckerle, D. E. Miller, M. E. Bertagnolli, S. J. Locke, Activation-dependent redistribution of the adhesion plaque protein, talin, in intact human platelets. The Journal of cell biology 109, 3333-3346 (1989); published online EpubDec (
• B. Franke, J. W. Akkerman, J. L. Bos, Rapid Ca2+-mediated activation of Rap1 in human platelets. EMBO J 16, 252-259 (1997); published online EpubJan 15 (10.1093/emboj/16.2.252).
• M. J. Berridge, M. D. Bootman, P. Lipp, Calcium--a life and death signal. Nature 395, 645-648 (1998); published online EpubOct 15 (10.1038/27094).
• P. Nicotera, S. Orrenius, The role of calcium in apoptosis. Cell calcium 23, 173-180 (1998); published online EpubFeb-Mar (
• K. Irie, A. Masuda, M. Shindo, Y. Nakagawa, H. Ohigashi, Tumor promoter binding of the protein kinase C C1 homology domain peptides of RasGRPs, chimaerins, and Unc13s. Bioorg Med Chem 12, 4575-4583 (2004); published online EpubSep 1 (10.1016/j.bmc.2004.07.008).
• J. E. Johnson, R. E. Goulding, Z. Ding, A. Partovi, K. V. Anthony, N. Beaulieu, G. Tazmini, R. B. Cornell, R. J. Kay, Differential membrane binding and diacylglycerol recognition by C1 domains of RasGRPs. Biochem J 406, 223-236 (2007); published online EpubSep 1 (10.1042/BJ20070294).
• C. W. Taylor, S. C. Tovey, IP(3) receptors: toward understanding their activation. Cold Spring Harbor perspectives in biology 2, a004010 (2010); published online EpubDec (10.1101/cshperspect.a004010).
• M. Spindler, J. M. M. van Eeuwijk, Y. Schurr, P. Nurden, B. Nieswandt, D. Stegner, A. Reinhold, M. Bender, ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet release and causes microthrombocytopenia. Blood 132, 635-646 (2018); published online EpubAug 9 (10.1182/blood-2018-01-829259).
• S. Dutting, F. Gaits-Iacovoni, D. Stegner, M. Popp, A. Antkowiak, J. M. M. van Eeuwijk, P. Nurden, S. Stritt, T. Heib, K. Aurbach, O. Angay, D. Cherpokova, N. Heinz, A. A. Baig, M. G. Gorelashvili, F. Gerner, K. G. Heinze, J. Ware, G. Krohne, Z. M. Ruggeri, A. T. Nurden, H. Schulze, U. Modlich, I. Pleines, C. Brakebusch, B. Nieswandt, A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis. Nat Commun 8, 15838 (2017); published online EpubJun 15 (10.1038/ncomms15838).
• L. Stefanini, R. H. Lee, D. S. Paul, E. C. O'Shaughnessy, D. Ghalloussi, C. I. Jones, Y. Boulaftali, K. O. Poe, R. Piatt, D. O. Kechele, K. M. Caron, K. M. Hahn, J. M. Gibbins, W. Bergmeier, Functional redundancy between RAP1 isoforms in murine platelet production and function. Blood, (2018); published online EpubAug 21 (10.1182/blood-2018-03-838714).
• M. P. Mahaut-Smith, D. Thomas, A. B. Higham, J. A. Usher-Smith, J. F. Hussain, J. Martinez-Pinna, J. N. Skepper, M. J. Mason, Properties of the demarcation membrane system in living rat megakaryocytes. Biophysical journal 84, 2646-2654 (2003); published online EpubApr (10.1016/S0006-3495(03)75070-X).
• S. K. Grange, "Technical note: Averaging wind speeds and directions (Research gate technical report)," (Research Gate, 2014). University Staff: Request a correction | Centaur Editors: Update this record |