Factor V is complexed with multimerin in resting platelet lysates and colocalizes with multimerin in platelet alpha-granules.
Factor V stored in platelets is an important source of factor Va for the prothrombinase complex. Investigations of potential platelet factor Va-binding proteins, using factor Va light chain affinity chromatography, identified a disulfide-linked multimeric protein with a reduced mobility of 155 kDa in the column eluate. Immunodepletion and immunoblotting indicated that this protein was multimerin. Multimerin specifically bound factors V and Va and the isolated factor Va light chain, but not the heavy chain of factor Va. Factor V stored in platelets, but not plasma factor V, was found to be complexed with multimerin. Multimerin immunodepletion of resting platelet lysates was associated with the removal of factor V and the loss of factor V coagulant activity. Immunoelectron microscopic studies colocalized factor V with multimerin in the alpha-granules of resting platelets. With thrombin-induced platelet activation, we observed dissociation of factor Va-multimerin complexes, multimerin-independent membrane binding of factor Va, and prothrombinase activity that was not inhibitable by multimerin antibodies. This study indicates that platelet factor V is stored as a complex with multimerin and suggests a possible role for multimerin as a carrier protein for factor V stored in platelets.
Hayward
C P
CP
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Furmaniak-Kazmierczak
E
E
Cieutat
A M
AM
Moore
J C
JC
Bainton
D F
DF
Nesheim
M E
ME
Kelton
J G
JG
Côté
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D001798:Blood Proteins / Q000276:immunology / Q000378:metabolism*; D002417:Cattle; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005165:Factor V / Q000378:metabolism*; D015943:Factor Va / Q000378:metabolism; D006801:Humans; D016253:Microscopy, Immunoelectron; D015539:Platelet Activation; D013925:Thromboplastin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001798:Blood Proteins; C069282:multimerin; D015943:Factor Va; D005165:Factor V; D013925:Thromboplastin