Analysis of Platelet Cytoskeleton Assembly during Platelet Activation in Hermansky-Pudlak Syndrome and Thrombasthenia

Summary

Time course change of the platelet cytoskeletal protein component in the Triton X-100 insoluble fraction after stimulation was analyzed in Hermansky-Pudlak syndrome and thrombasthenia.

In Hermansky-Pudlak syndrome (HPS), a 31 kDa protein, myosin, actin, and a 100 kDa protein assembled as in the normal platelets at the shape change and release reaction phases after ADP or collagen stimulation, suggesting that, the deficient dense granule content do not lead to an abnormal platelet cytoskeletal protein assembly. In thrombasthenia (Type I), myosin increased at the shape change and release reaction phases as it does in normal platelets, but actin and the 100 kDa protein increased only at the initial activation phase, and then subsequently decreased to the level of the resting phase. The actin-binding protein (ABP) and the 31 kDa protein increased a little following stimulation. Similar cytoskeletal protein change after stimulation were found in normal platelets which were prevented from the aggregation process by chelating the external Ca²⁺ or by using synthetic decapeptide of fibrinogen γ-chain of carboxyl terminus. The decreased platelet cytoskeletal protein assembly in thrombasthenia or in platelets stimulated without aggregation, was derived from a loss of the platelet aggregation process due to the defect of GP Ilb-IIIa complex or an interaction failure between GP IIb-IIIa complex and fibrinogen. The interaction between platelets and either fibrinogen or fibrin can induce a more stable platelet cytoskeletal protein assembly, however, agonistic stimulation without these interactions cannot do it directly.

Keywords

Hermansky-Pudlak Sydrome - Thrombasthenia - Platelet cytoskeleton - Intercation of platelet and fibrinogen

• References

• 1 Phillips DR, Jennings LK, Edwards HH. Identification of membrane proteins mediating the interaction of human platelets. J Cell Biol 1980; 86: 77-86
• 2 Jennings LK, Fox JE B, Edwards HH, Phillips DR. Changes in the cytoskeletal structure of human platelets following thrombin activation. J Biol Chem 1981; 256: 6927-6932
• 3 Painter RG, Ginsberg M. Concanavalin A induces interactions between surface glycoproteins and the platelet cytoskeleton. J Cell Biol 1982; 92: 565-573
• 4 Fujimura K, Maehama S, Kuramoto A. Correlation between platelet membrane glycoproteins and contractile proteins associated with thrombin induced platelet aggregation. Acta Haematol jpn 1982; 45: 1346-1354
• 5 Wheeler ME, Cox AC, Caroll RC. Retention of the glycoprotein IIb -IIIa complex in the isolated platelet cytoskeleton. J Clin Invest 1984; 74: 1080-1089
• 6 Lind SE, Stossel TP. The microfilament network of the platelet. In: Progress in Hemostasis and Thrombosis. Vol. 6 Spaet TH. ed Grune and Stratton; New York: 1982: 63-84
• 7 Fox JE B, Phillips DR. Polymerization and organization of actin filaments within platelets. Sem Hematol 1983; 20: 243-260
• 8 Nachmias VT. Platelet and Megakaryocyte shape change: Triggered alterations in the cytoskeleton. Sem Hematol 1983; 20: 261-281
• 9 Nachmias VT. Cytoskeleton of human platelets at rest and after spreading. J Cell Biol 1980; 86: 795-802
• 10 Weiss II J, Hervenick PA, Zalusky R, Factor A. A familial defect in platelet function associated with impaired release of adenosine diphosphate. N Eng J Med 1969; 281: 1264-1270
• 11 Weiss HJ, Witte LD, Kaplan KL, Lages BA, Chernoff A, Nossel HL, Goodman DS, BaumgartnerII R. Heterogeneity in stoiagc pool deficiency Studies on granule-bound substances in 18 patients including variants deficient in a-granules, platelet factor 4, p-thromboglobulin, and platelet-derived growth factor. Blood 1979; 54: 1296-1319
• 12 Nurden AT, Caen JP. Specific roles for platelet surface glycoproteins in platelet function. Nature (London) 1975; 255: 720-722
• 13 Phillips DR, Agin PP. Platelet membrane defects in Glanzmann’s thrombasthenia. Evidence for decreased amounts of two major glycopioteins. J Clin Invest 1977 60. 535-545
• 14 Tangen O, Berman HJ, Marfey P. Gel filtration, a new technique for separation of blood platelets from plasma. Thromb Diath Haemorrh 1971; 25: 268-278
• 15 Born GV R. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature (London) 1962; 194: 927-929
• 16 Charo IF, Feinman RD, Detwiler TC. Interrelations of platelet aggregation and secretion. J Clin Invest 1977; 60: 866-873
• 17 Laemmli UD. Cleavage of structural proteins during the assembly of head of bacteriophage T₄ . Nature (London) 1970; 227: 680-685
• 18 Carlsson L, Markey F, Blikstad I, Persson T, Lindberg U. Reorganization of actin in platelets stimulated by thrombin as measured by the DNase I inhibition assay. Proc Natl Acad Sci USA 1979; 76: 6376-6380
• 19 Chaponnier C, Borgia R, Rungger-Brandle E, Weil R, Gabbiani G. An actin-destabilizing factor is present in human plasma. Experientia 1979; 35: 1039-1041
• 20 Marris HE, Gooch J. An actin depolymerizing protein from pig plasma. FEBS Lett 1981; 123: 49-53
• 21 Fox JE B, Phillips DR. Role of phosphorylation in mediating the association of myosin with the cytoskeletal structures of human platelets. J Biol Chem 1982; 257: 4120-4126
• 22 Lyons RM, Staford N, Majerus PW. Thrombin-induced protein phosphorylation in human platelets. J Clin Invest 1975; 56: 924-936
• 23 Daniel JL, Molish IR, Holmsen H. Myosin phosphorylation in intact platelets. J Biol Chem 1981; 256: 7510-7514
• 24 Haslam RJ, Lynham JA. Relationship between phosphorylation of blood platelet proteins and secretion of platelet granule constituents. I. Effects of different aggregation agents. Biochem Biophys Res Commun 1977 77. 714-722
• 25 Haslam RJ, Lynham JA, Fox JE B. Effects of collagen. Ionophore A23187 and prostaglandin E, on the phosphorylation of specific proteins in blood platelets Biochem J 1979; 178: 397-406
• 26 Daniel JL, Molish IR, Rigmaiden M, Stewart G. Evidence for a role of myosin phosphorylation in the initiation of the platelet shape change response. J Biol Chem 1984; 259: 9826-9831
• 27 Lorez HP, Richards JG, DaPrada M, Picotti GB, Pareti FI, Capitanio A, Mannucci PM. Storage pool disease; Comparative fluorescence microscopical, cytochemical and biochemical studies on aminestoring organelles of human blood platelets. Br J Haematol 1979; 43: 297-305
• 28 Nunez D, Levy-Toledano S. Further characterization of human platelet activation in the absence of aggregation: phosphorylations of specific proteins and relationship with platelet secretion. Thromb Haemostas 1984; 51: 198-203
• 29 Zhuang Qing-Qi, Rosenberg S, Lawrence J, Stracher A. Role of actin binding protein phosphorylation in platelet cytoskeleton assembly. Bioch Biophys Res Commun 1984; 118: 508-513
• 30 Carroll RC, Butler RG, Morris PA. Separable assembly of platelet pseudopodal and contractile cytoskeletons. Cell 1982; 30: 385-393
• 31 Carroll RC, Gerrard JM. Phosphorylation of platelet actin binding protein during platelet activation. Blood 1982; 59: 466-471
• 32 Tuszynski GP, Kornecki E, Cierniewski CS, Knight LC, Koshy A, Strivastave S, Niewiarowski S, Walsh PN. Association of fibrin with the platelet cytoskeleton. J Biol Chem 1984; 259: 5247-5254
• 33 Niewiarowski J, Cierniewski CS, Tuszynski GP. Association of fibronectin with the platelet cytoskeleton. J Biol Chem 1984; 259: 6181
• 34 Plow EF, Ginsberg M. Specific and saturable binding of plasma fibronectin to thrombin-stimulated human platelets. J Biol Chem 1981; 256: 9477-9482
• 35 Parise LV, Phillips DR. Reconstitution of the purified platelet fibrinogen receptor. Fibrinogen binding properties of the glycoprotein IIb-IIIa complex. J Biol Chem 1985; 260: 10698-10707
• 36 Cohen I, Gerrard JM, White JG. Ultrastructure of clots during isometric contraction. J Cell Biol 1982; 93: 775-787