Megakaryocyte-specific RhoA deficiency causes macrothrombocytopenia and defective platelet activation in hemostasis and thrombosis

Blood

Volumn 119, Issue 4, 2012, Pages 1054-1063

  Pleines, Irina ^a   Hagedorn, Ina ^a   Gupta, Shuchi ^a   May, Frauke ^a   Chakarova, Lidija ^a   Van Hengel, Jolanda ^b   Offermanns, Stefan ^c   Krohne, Georg ^d   Kleinschnitz, Christoph ^e   Brakebusch, Cord ^f   Nieswandt, Bernhard ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b GHENT UNIVERSITY   (Belgium)

^c MAX PLANCK INSTITUTE FOR HEART AND LUNG RESEARCH   (Germany)

^d UNIVERSITY OF WÜRZBURG   (Germany)

^e UNIVERSITY OF WÜRZBURG   (Germany)

^f UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

FIBRINOGEN; GUANINE NUCLEOTIDE BINDING PROTEIN; INTEGRIN; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLEEDING TIME; BLOOD CLOT RETRACTION; CONTROLLED STUDY; DEGRANULATION; FEMALE; GENE; GENE DELETION; HEMOSTASIS; IN VITRO STUDY; IN VIVO STUDY; MALE; MEGAKARYOCYTE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN SUBUNIT; RHOA GENE; SIGNAL TRANSDUCTION; THROMBOCYTE FUNCTION; THROMBOCYTE SHAPE; THROMBOCYTOPENIA; THROMBOSIS;

EID: 84863011162     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2011-08-372193     Document Type: Article

References (52)

1. Jaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005;21:247- 269.
2. Bustelo XR, Sauzeau V, Berenjeno IM. GTP-binding proteins of the Rho/Rac family: regulation, effectors and functions in vivo. Bioessays. 2007;29(4):356-370. (Pubitemid 46597867)
3. Watanabe T, Noritake J, Kaibuchi K. Regulation of microtubules in cell migration. Trends Cell Biol. 2005;15(2):76-83. (Pubitemid 40188217)
4. Piekny A, Werner M, Glotzer M. Cytokinesis: welcome to the Rho zone. Trends Cell Biol. 2005; 15(12):651-658. (Pubitemid 41713966)
5. Offermanns S. Activation of platelet function through G protein-coupled receptors. Circ Res. 2006;99(12):1293-1304. (Pubitemid 44949665)
6. Moers A, Nieswandt B, Massberg S, et al. G13 is an essential mediator of platelet activation in hemostasis and thrombosis. Nat Med. 2003;9(11): 1418-1422. (Pubitemid 37466193)
7. Klages B, Brandt U, Simon MI, Schultz G, Offermanns S. Activation of G12/G13 results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. J Cell Biol. 1999;144(4):745-754. (Pubitemid 29234552)
8. Gratacap MP, Payrastre B, Nieswandt B, Offermanns S. Differential regulation of Rho and Rac through heterotrimeric G-proteins and cyclic nucleotides. J Biol Chem. 2001;276(51):47906- 47913.
9. Moers A,Wettschureck N, Gruner S, Nieswandt B, Offermanns S. Unresponsiveness of platelets lacking both Galpha(q) and Galpha(13). Implications for collagen-induced platelet activation. J Biol Chem. 2004;279(44):45354-45359. (Pubitemid 39491518)
10. Suzuki Y, Yamamoto M, Wada H, et al. Agonist-induced regulation of myosin phosphatase activity in human platelets through activation of Rhokinase. Blood. 1999;93(10):3408-3417. (Pubitemid 29220908)
11. Paul BZ, Daniel JL, Kunapuli SP. 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. 1999;274(40):28293-28300.
12. Bauer M, Retzer M, Wilde JI, et al. Dichotomous regulation of myosin phosphorylation and shape change by Rho-kinase and calcium in intact human platelets. Blood. 1999;94(5):1665-1672. (Pubitemid 29411316)
13. Bodie SL, Ford I, Greaves M, Nixon GF. Thrombin-induced activation of RhoA in platelet shape change. Biochem Biophys Res Commun. 2001;287(1):71-76. (Pubitemid 32912464)
14. Huang JS, Dong L, Kozasa T, Le Breton GC. Signaling through G(alpha)13 switch region I is essential for protease-activated receptor 1-mediated human platelet shape change, aggregation, and secretion. J Biol Chem. 2007;282(14):10210- 10222.
15. Leng L, Kashiwagi H, Ren XD, Shattil SJ. RhoA and the function of platelet integrin alphaIIbbeta3. Blood. 1998;91(11):4206-4215. (Pubitemid 28261984)
16. Missy K, Plantavid M, Pacaud P, et al. Rhokinase is involved in the sustained phosphorylation of myosin and the irreversible platelet aggregation induced by PAR1 activating peptide. Thromb Haemost. 2001;85(3):514-520. (Pubitemid 32233028)
17. Schoenwaelder SM, Hughan SC, Boniface K, et al. RhoA sustains integrin alpha IIbbeta 3 adhesion contacts under high shear. J Biol Chem. 2002;277(17):14738-14746. (Pubitemid 34952545)
18. Gong H, Shen B, Flevaris P, et al. G protein sub-unit Galpha13 binds to integrin alphaIIbbeta3 and mediates integrin "outside-in" signaling. Science. 2010;327(5963):340-343.
19. Heasman SJ, Ridley AJ. Mammalian Rho GT-Pases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol. 2008;9(9): 690-701.
20. Jackson B, Peyrollier K, Pedersen E, et al. RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes. Mol Biol Cell. 2011;22(5):593-605.
21. Tiedt R, Schomber T, Hao-Shen H, Skoda RC. Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo. Blood. 2007;109(4):1503-1506. (Pubitemid 46239582)
22. Knight CG, Morton LF, Onley DJ, et al. Collagen-platelet interaction: Gly-Pro-Hyp is uniquely specific for platelet Gp VI and mediates platelet activation by collagen. Cardiovasc Res. 1999;41(2): 450-457. (Pubitemid 29087341)
23. Nieswandt B, Bergmeier W, Rackebrandt K, Gessner JE, Zirngibl H. Identification of critical antigen-specific mechanisms in the development of immune thrombocytopenic purpura in mice. Blood. 2000;96(7):2520-2527.
24. Pleines I, Eckly A, Elvers M, et al. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. Blood. 2010;115(16):3364-3373.
25. Braun A, Varga-Szabo D, Kleinschnitz C, et al. Orai1 (CRACM1) is the platelet SOC channel and essential for pathological thrombus formation. Blood. 2009;113(9):2056-2063.
26. Elvers M, Stegner D, Hagedorn I, et al. Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1. Sci Signal. 2010;3(103):ra1.
27. May F, Hagedorn I, Pleines I, et al. CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis. Blood. 2009;114(16):3464- 3472.
28. Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986;17(3):472-476. (Pubitemid 16085691)
29. 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(42):39493-39498. (Pubitemid 35190926)
30. Stegner D, Nieswandt B. Platelet receptor signaling in thrombus formation. J Mol Med. 2011;89(2): 109-121.
31. Gao G, Chen L, Dong B, et al. RhoA effector mDia1 is required for PI 3-kinase-dependent actin remodeling and spreading by thrombin in platelets. Biochem Biophys Res Commun. 2009; 385(3):439-444.
32. Cohen I. The contractile system of blood platelets and its function. Methods Achiev Exp Pathol. 1979;9:40-86.
33. Morgenstern E, Ruf A, Patscheke H. Ultrastructure of the interaction between human platelets and polymerizing fibrin within the first minutes of clot formation. Blood Coagul Fibrinolysis. 1990; 1(4-5):543-546.
34. Jackson SP, Nesbitt WS, Westein E. Dynamics of platelet thrombus formation. J Thromb Haemost. 2009;(7 suppl 1):117-120.
35. Kleinschnitz C, Pozgajova M, Pham M, et al. 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(17):2323- 2330.
36. Stoll G, Kleinschnitz C, Nieswandt B. Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood. 2008;112(9):3555-3562.
37. Nieswandt B, Kleinschnitz C, Stoll G. Ischaemic stroke: a thrombo-inflammatory disease? J Physiol. 2011;589(17):4115-4123.
38. Chen Z, Naveiras O, Balduini A, et al. The May- Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho- ROCK pathway. Blood. 2007;110(1):171-179. (Pubitemid 47026832)
39. Chang Y, Aurade F, Larbret F, et al. Proplatelet formation is regulated by the Rho/ROCK pathway. Blood. 2007;109(10):4229-4236. (Pubitemid 46743387)
40. Vogt S, Grosse R, Schultz G, Offermanns S. Receptor-dependent RhoA activation in G12/ G13-deficient cells: genetic evidence for an involvement of Gq/G11. J Biol Chem. 2003; 278(31):28743-28749. (Pubitemid 36935782)
41. Riondino S, Lotti LV, Cutini L, Pulcinelli FM. Collagen-induced platelet shape change is not affected by positive feedback pathway inhibitors and cAMP-elevating agents. J Biol Chem. 2005; 280(8):6504-6510. (Pubitemid 40341199)
42. Jin J, Mao Y, Thomas D, et al. RhoA downstream of G(q) and G(12/13) pathways regulates protease- activated receptor-mediated dense granule release in platelets. Biochem Pharmacol. 2009; 77(5):835-844.
43. Ory S, Gasman S. Rho GTPases and exocytosis: what are the molecular links? Semin Cell Dev Biol. 2011;22(1):27-32.
44. Reed GL, Fitzgerald ML, Polgar J. Molecular mechanisms of platelet exocytosis: insights into the "secrete" life of thrombocytes. Blood. 2000; 96(10):3334-3342.
45. Lutz S, Shankaranarayanan A, Coco C, et al. Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoAby GPCRs. Science. 2007;318(5858):1923-1927.
46. Dorsam RT, Kim S, Jin J, Kunapuli SP. Coordinated signaling through both G12/13 and G(i) pathways is sufficient to activate GPIIb/IIIa in human platelets. J Biol Chem. 2002;277(49):47588- 47595.
47. Melendez J, Stengel K, Zhou X, et al. RhoA GT-Pase is dispensable for actomyosin regulation but is essential for mitosis in primary mouse embryonic fibroblasts. J Biol Chem. 2011;286(17): 15132-15137.
48. Nemoto Y, Namba T, Teru-uchi T, et al. A rho gene product in human blood platelets. I. Identification of the platelet substrate for botulinum C3 ADP-ribosyltransferase as rhoA protein. J Biol Chem. 1992;267(29):20916-20920.
49. Higashi T, Ikeda T, Shirakawa R, et al. Biochemical characterization of the Rho GTPase-regulated actin assembly by diaphanous-related formins, mDia1 and Daam1, in platelets. J Biol Chem. 2008;283(13):8746-8755.
50. Gad AK, Aspenstrom P. Rif proteins take to the RhoD: Rho GTPases at the crossroads of actin dynamics and membrane trafficking. Cell Signal. 2010;22(2):183-189.
51. Paul BZ, Kim S, Dangelmaier C, et al. Dynamic regulation of microtubule coils in ADP-induced platelet shape change by p160ROCK (Rhokinase). Platelets. 2003;14(3):159-169. (Pubitemid 36609808)
52. Althaus K, Greinacher A. MYH9-related platelet disorders. Semin Thromb Hemost. 2009;35(2): 189-203.