title: The storage defects in grey platelet syndrome and alphadelta-storage pool deficiency affect alpha-granule factor V and multimerin storage without altering their proteolytic processing.
abstract: Among proteins stored in alpha-granules, multimerin and factor V share unusual features: they bind to each other, are proteolysed to unique forms and are stored eccentrically in alpha-granules. These unique features of their processing led us to study these proteins in alpha delta storage pool deficiency (alphadelta-SPD) and grey platelet syndrome (GPS, alpha-SPD), two conditions known to impair alpha-granule protein storage. Platelet factor V and multimerin were severely reduced in GPS, whereas they ranged from reduced to normal in alphadelta-SPD. The platelet levels of factor V and multimerin in these disorders indicated multimerin deficiency was not predictive of platelet factor V deficiency, although it reduced the amount of multimerin associated with platelet factor V. In GPS only, the defect in storing proteins was associated with increased multimerin and multimerin-factor V complexes in plasma. Like normal platelets, GPS and alphadelta-SPD platelets contained factor V mainly in granules. Platelet factor V and multimerin were proteolysed to normal platelet forms in GPS and alphadelta-SPD platelets, indicating that these conditions preserve some aspects of normal alpha-granule protein processing. Although we found factor V can be stored in platelets deficient in multimerin, our data indicate that multimerin storage influences the point at which multimerin binds factor V.
authors.affiliation: Departments of Pathology and Molecular Medicine and Medicine, McMaster University and the Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada. haywrdc@mcmaster.ca
authors.forename: C P
authors.initials: CP
authors.lastname: Hayward
authors.forename: H J
authors.initials: HJ
authors.lastname: Weiss
authors.forename: B
authors.initials: B
authors.lastname: Lages
authors.forename: M
authors.initials: M
authors.lastname: Finlay
authors.forename: A C
authors.initials: AC
authors.lastname: Hegstad
authors.forename: S
authors.initials: S
authors.lastname: Zheng
authors.forename: A
authors.initials: A
authors.lastname: Cowie
authors.forename: J M
authors.initials: JM
authors.lastname: Massé
authors.forename: P
authors.initials: P
authors.lastname: Harrison
authors.forename: E M
authors.initials: EM
authors.lastname: Cramer
mesh_terms: D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D005165:Factor V / Q000032:analysis / Q000378:metabolism*; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D016253:Microscopy, Immunoelectron; D010981:Platelet Storage Pool Deficiency / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000032:analysis
chemical_list: D001798:Blood Proteins; D019700:Thrombospondin 1; C069282:multimerin; D005165:Factor V; D005340:Fibrinogen