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DOI: 10.1160/TH03-02-0123
Human platelets contain forms of factor V in disulfide-linkage with multimerin
Financial support: Supported by grant 42450 from the Canadian Institutes of Health Research (C.P.M. Hayward) and grants HL43106 and HL54939 from the National Institutes of Health (W.H. Kane). C.P.M. Hayward is the recipient of a Career Investigator Award from the Heart and Stroke Foundation of Ontario and a Canada Research Chair in Molecular Hemostasis. Samira B. Jeimy is the recipient of a Heart and Stroke Foundation of Ontario Research Master’s Studentship Award.Publication History
Received
27 February 2003
Accepted after revision
17 September 2004
Publication Date:
02 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200406/lookinside/thumbnails/10-1160-th03-02-0123-1.jpg)
Summary
Factor V is an essential cofactor for blood coagulation that circulates in platelets and plasma. Unlike plasma factor V, platelet factorV is stored complexed with the polymeric α-granule protein multimerin. In analyses of human platelet factor V on nonreduced denaturing multimer gels, we identified that approximately 25% was variable in size and migrated larger than single chain factor V, the largest form in plasma. Upon reduction, the unusually large, variably-sized forms of platelet factor V liberated components that comigrated with other forms of platelet factor V, indicating that they contained factor V in interchain disulfide-linkages. With thrombin cleavage, factor Va heavy and light chain domains, but not B-domains, were liberated from the components linked by interchain disulfide bonds, indicating that the single cysteine in the B-domain at position 1085 was the site of disulfide linkage. Since unusually large factor V had a variable size and included forms larger than factor V dimers, the data suggested disulfide-linkage with another platelet protein, possibly multimerin. Immunoprecipitation experiments confirmed that unusually large factor V was associated with multimerin and it remained associated in 0.5 M salt. Moreover, platelets contained a subpopulation of multimerin polymers that resisted dissociation from factor V by denaturing detergent and comigrated with unusually large platelet factor V, before and after thrombin cleavage.The disulfide-linked complexes of multimerin and factor V in platelets, which are cleaved by thrombin to liberate factor Va, could be important for modulating the function of platelet factor V and its delivery onto activated platelets. Factor Va generation and function from unusually large platelet factor V is only speculative at this time.
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