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.
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.
Hayward
C P
CP
Departments of Pathology and Molecular Medicine and Medicine, McMaster University and the Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada. haywrdc@mcmaster.ca
Weiss
H J
HJ
Lages
B
B
Finlay
M
M
Hegstad
A C
AC
Zheng
S
S
Cowie
A
A
Massé
J M
JM
Harrison
P
P
Cramer
E M
EM
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
D001798:Blood Proteins; D019700:Thrombospondin 1; C069282:multimerin; D005165:Factor V; D005340:Fibrinogen