Identification of Dense Granule Specific Membrane Proteins in Bovine Platelets that Are Absent in the Chediak-Higashi Syndrome

Summary

Platelets from cattle with the Chediak-Higashi syndrome (CHS) have a platelet dense granule deficiency. One hypothesis for the platelet dense granule deficiency is that the granule is simply not formed in CHS megakaryocytes (MK). Alternative hypotheses include that the granule is assembled in CHS MK but a functional amino-nucleotide-cation storage complex cannot be formed or that the dense granule or its precursor fuses with other granules. This study was undertaken to determine if membrane proteins specific for platelet dense granules can be identified in membranes of other granules in CHS platelets. Platelets were disrupted; a mixed-granule fraction and alpha-granule enriched, mitochondrial-enriched, and dense granule-enriched subfractions were obtained. Membrane proteins in these intact granules were radiolabeled and the granule underwent hypotonic lysis. Membrane proteins were extracted from granule “ghosts”, separated, and then visualized by autoradiography. Three major proteins were identified in platelet dense granule membrane subfractions. Two of these proteins could be identified in membrane extracts from the mixed-granule fraction from normal platelets. They could neither be identified in extracts from the mixed granule fraction of CHS platelets nor in membranes from alpha granule-enriched and mitochondrial-enriched subfractions. The absence of dense granule membrane proteins in membranes of other organelles within CHS platelets suggests that fusion of dense granules or its precursor with other granules cannot account for the platelet dense granule deficiency in CHS platelets.

• References

• 1 Bell TG, Meyers KM, Prieur DJ, Fauci AS, Wolf SW, Padgett GA. Decreased nucleotide and serotonin storage associated with defective function in Chediak-Higashi syndrome cattle and human platelets. Blood 1976; 48: 175-84
• 2 Buchanan MF, Handin RI. Platelet function in the Chediak-Higashi syndrome. Blood 1976; 47: 941-948
• 3 Costa JL, Fauci AS, Wolf SM. A platelet abnormality in the Chediak-Higashi syndrome of man. Blood 1976; 48: 517-520
• 4 Boxer GJ, Holmsen H, Robkin L, Bank NU, Boxer LA, Baehner RL. Abnormal platelet functions in the Chediak-Higashi syndrome. Br J Haematol 1977; 35: 521-533
• 5 Parmely RT, Poon MC, Crist WM, Malhuh A. Giant platelet granules in a child with the Chediak-Higashi syndrome. Am J Hematol 1979; 6: 51-60
• 6 Rendu F, Brenton-Gorius J, Lebert M, Klebanoff C, Buriot D, Griscelli C, Levy-Toledano S, Caen JP. Evidence that abnormal platelet functions in human Chediak-Higashi syndrome are the results of a lack of dense bodies. Am J Pathol 1983; 111: 309-314
• 7 Apitz-Castro R, Cruz MR, Ledezman E, Merino F, Ramerez-Duque P, Dangelmeier C, Holmsen H. The storage pool deficiency in platelets from humans with the Chediak-Higashi syndrome. Br J Haematol 1985; 59: 471-483
• 8 Meyers KM, Stevens D, Padgett GA. A platelet serotonin anomaly in the Chediak-Higashi syndrome. Res Commun Chem Pathol Pharmacol 1974; 2: 375-380
• 9 Meyers KM, Holmsen H, Seachord CL, Hopkins GE, Borchard RE, Padgett GA. Storage pool deficiency in platelets from Chediak-Higashi cattle. Am J Physiol 1979; 237: 239-248
• 10 Meyers KM, Holmsen H, Seachord CL, Hopkins G, Gorham J. Characterization of platelets from normal mink and mink with the Chediak-Higashi syndrome. Am J Hematol 1979; 7: 137-146
• 11 Meyers KM, Seachord CL, Holmsen H, Prieur DJ. Evaluation of the platelet storage pool deficiency in the feline counterpart of the Chediak-Higashi syndrome. Am J Hematol 1981; 11: 241-253
• 12 Meyers KM, Hopkins G, Holmsen H, Benson K, Prieur DJ. Ultrastructure of resting and activated storage pool deficient platelets from animals with the Chediak-Higashi syndrome. Am J Pathol 1982; 106: 364-377
• 13 Fagerland JA, Hagemoser WA, Ireland WP. Ultrastructure and serology of leukocytes and platelets of normal foxes and a fox with a Chediak-Higashi-like syndrome. Vet Pathol 1987; 24: 164-169
• 14 White JG, Clawson CC. Chediak-Higashi syndrome: variable cytochemical reactivity of giant inclusions in polymorphonuclear leukocytes. Ultrastruct Pathol 1980; 11: 223-226
• 15 Meyers KM, Seachord CL, Benson K, Fukami M, Holmsen H. Serotonin accumulation in granules of storage pool deficient platelets of Chediak-Higashi cattle. Am J Physiol 1983; 245 H 150-158
• 16 Menard M, Meyers KM. Storage pool deficiency in cattle with the Chediak-Higashi syndrome results from an absence of dense granule precursors in their megakaryocytes. Blood 1988; 72: 1726-1734
• 17 Fukami MH, Bauer JS, Steward GJ, Salganicoff L. An improved method for the isolation of dense storage granules from human platelets. J Cell Biol 1978; 77: 389-399
• 18 Daniel JL, Molish IR, Holmsen H. Myosin phosphorylation in intact platelets. J Biol Chem 1981; 256: 7510-7514
• 19 Lasky RA, Mills AD. Enhanced autoradiographic detection of ³²P and ¹²⁵I using intensifying screens and hypersensitive film. FEBS Lett 1977; 82: 314-316
• 20 Van der Meulen J, Furuya W, Grinstein S. Isolation and partial characterization of platelet alpha-granule membranes. J Memb Biol 1983; 71: 47-59
• 21 Rudnick GH, Fishkes H, Nelson PJ, Schuldiner S. Evidence for two distinct serotonin transport systems in platelets. J Biol Chem 1980; 255: 4631-4635
• 22 Lages B, Scrutton M, Holmsen H, Day HJ, Weiss HJ. Metal ion content of gel-filtered platelets from patients with storage pool disease. J Lab Clin Med 1975; 90: 873-882
• 23 Meyers KM, Holmsen H, Seachord CL. Comparative study of platelet dense granule constituents. Am J Physiol 1982; 243 R 454-461
• 24 Holmsen H, Day HJ. Adenine nucleotides and platelet function. Ser Hematol 1971; 4: 28-58
• 25 Hutton JC. The internal pH and membrane potential of the insulin secretory granule. Biochem J 1982; 204: 171-178
• 26 Xei X-S, Stone DK, Racker E. Determinants of clathrin-coated vesicle acidification. J Biol Chem 1983; 258: 14834-14838
• 27 Johnson RG, Beers MF, Scarpa A. H⁺-ATPase of chromaffin granules. J Biol Chem 1982; 257: 10701-10707
• 28 Gabizon R, Yetinson T, Schuldiner S. Photoinactivation and identification of biogenic amine transporter in chromaffin granules from bovine adrenal medulla. J Biol Chem 1982; 257: 15145-15150
• 29 Gabizon R, Schuldiner S. The amine transporter fom bovine chromaffin granules. J Biol Chem 1985; 260: 3001-3005
• 30 Kostron H, Winkler H, Peer LJ, Konig P. Uptake of adenosine triphosphate by isolated chromaffin granules: a carrier-mediated process. Neurosci 1977; 2: 159-166
• 31 Kostron H, Winkler H, Geissler D, Konig P. Uptake of calcium by chromaffin granules in vitro. J Neurochem 1977; 28: 487-493
• 32 Winkler H, Apps DK, Fischer-Colbrie R. The molecular function of adrenal chromaffin granules. Neurosci 1986; 18: 261-290
• 33 Bjerrum OJ, Helle KB, Bock E. Immunochemically identical hydrophilic and amphilic forms of the bovine adrenomedullary dopamine b-hydroxylase. Biochem J 1979; 181: 231-237
• 34 Winkler H, Westhead E. The molecular organization of adrenal chromaffin granules. Neurosci 1980; 5: 1803-1823
• 35 Srivastava M, Duong LT, Fleming PJ. Cytochrome b-561 catalyzes transmembrane electron transfer. J Biol Chem 1984; 259: 8072-8075
• 36 Johnson RG, Scarpa A. The electon transport chain of serotonin-dense granules of platelets. J Cell Biol 1981; 256: 11966-11969
• 37 Flatmark T, Grongberg M. Cytochrome b-561 of the bovine adrenal chromaffin granules. Biochem Biophys Res Commun 1981; 99: 292-301
• 38 Duong LT, Fleming PJ. Isolation and properties of Cytochrome b-561 from bovine adrenal chromaffin granules. J Biol Chem 1982; 257: 8561-8564
• 39 Gavine FS, Pryde JG, Deane DL, Apps DK. Glycoproteins of the chromaffin granule membrane: separation by two-dimensional electrophoresis and identification by lectin binding. J Neurochem 1984; 43: 1243-1252
• 40 Huber E, Konig P, Schuler G, Aberer W, Plattner H, Winkler H. Characterization and topography of the glycoproteins of adrenal chromaffin granules. J Neurochem 1979; 32: 35-47
• 41 Rendu F, Lebret M, Danielian S, Fagard R, Levy-Toledano S, Fischer S. High pp60c-src level in human platelet dense bodies. Blood 1989; 73: 1545-1551
• 42 Philips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb-IIIa complex. Blood 1988; 71: 831-843
• 43 Gogstad GO, Hagen I, Korsmo R, Solum NO. Characterization of the proteins of isolated human platelet alpha-granules. Biochim Biophys Acta 1981; 670: 150-162
• 44 Woods VL, Wolff LE, Keller DM. Resting platelets contain a substantial centrally located pool of glycoprotein Ilb-IIIa complex which may be accessible to some but not other extracellular proteins. J Biol Chem 1986; 261: 15242-15251
• 45 Wencel-Drake JD, Plow EF, Kunicki TJ, Woods VL, Keller DM, Ginsberg MH. Localization of internal pools of membrane glycoproteins involved in platelet adhesive responses. Am J Pathol 1986; 124: 324-334
• 46 Phillips DR, Agin PP. Platelet plasma membrane glycoproteins. J Biol Chem 1977; 252: 2121-2126
• 47 McEver RP, Martin MN. A monoclonal antibody to a membrane glycoproteins binds only to activated platelets. J Biol Chem 1984; 259: 9799-9804
• 48 Hsu-Lin S-C, Berman CL, Furie BC, August D, Furie B. A platelet membrane protein expressed during platelet activation and secretion. J Biol Chem 1984; 259: 9121-9126
• 49 Stenberg PE, McEver RP, Shuman MA, Jacques YV, Bainton DF. A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J Cell Biol 1984; 259: 9799-9804
• 50 Berman CL, Yeo EL, Wencel-Drake D, Fuire BC, Ginsberg MH, Furie B. A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. J Clin Invest 1986; 78: 130-137
• 51 Johnstone GI, Cook RG, McEver RP. Cloning of GMP-140, a granule membrane protein of platelets and endothelium. Cell 1989; 56: 1033-1044
• 52 Carrell NA, Fitzgerald LA, Steiner B, Erickson HP, Phillips DR. Structure of human platelet membrane glycoproteins IIb and IIIa as determined by electron microscopy. J Biol Chem 1895; 260: 1743-1749
• 53 Zucker-Franklin D, Benson K, Meyers KM. Absence of a surface-connected canalicular system in bovine platelets. Blood 1985; 65: 241-244
• 54 Rosa J-P, George JN, Bainton DF, Nurden AT, Caen JP, McEver RP. Gray platelet syndrome: demonstration of alpha granule membranes that can fiise with the cell surface. J Clin Invest 1987; 80: 1138-1146
• 55 Santos MJ, Imanaka T, Shio H, Lazarow PB. Peroxisomal integral membrane proteins in control and Zellweger fibroblasts. J Biol Chem 1988; 263: 10502-10509
• 56 Santos MJ, Imanaka T, Shio H, Small GM, Lazarow PB. Peroxisomal membrane ghosts in Zellweger syndrome-aberrant organelle assembly. Science 1988; 239: 1536-1538
• 57 Spicer SS, Sato A, Vincent R, Eguchi ME, Poon KC. Lysosome enlargement in the Chediak-Higashi syndrome. Fed Proc 1981; 40: 1451-1455