Endocytosis and storage of plasma factor V by human megakaryocytes.
Factor V is an essential coagulation cofactor that circulates in plasma and platelet alpha-granules where it is stored complexed to multimerin I (MMRN1). To gain insights into the origin and processing of human platelet factor V, and factor V-MMRN I complexes, we studied factorV in cultured megakaryocytes. Factor V mRNA was detected in all megakaryocyte cultures. However, like albumin, IgG and fibrinogen, factorV protein was detectable only in megakaryocytes cultured with exogenous protein. The amount of factor V associated with megakaryocytes was influenced by the exogenous factorV concentration. Similar to platelet factor V, megakaryocyte factor V was proteolyzed and complexed with megakaryocyte-synthesized MMRN1. With secretagogues, megakaryocytes released factor V, IgG, fibrinogen and MMRN1. Immunofluorescent and electron microscopy confirmed factorV uptake by endocytosis and its trafficking to megakaryocyte alpha-granules. These data provide direct evidence that human megakaryocytes process plasma-derived factor V into alpha-granules and generate factorV-MMRN I complexes from endogenously and exogenously synthesized proteins.
Suehiro
Youko
Y
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Veljkovic
Dragoslava Kika
DK
Fuller
Nola
N
Motomura
Yasuaki
Y
Massé
Jean Marc
JM
Cramer
Elisabeth M
EM
Hayward
Catherine P M
CP
D001792:Blood Platelets / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D004705:Endocytosis; D005165:Factor V / Q000235:genetics / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008533:Megakaryocytes / Q000378:metabolism*; D010949:Plasma / Q000378:metabolism; D040201:Platelet Membrane Glycoprotein IIb / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors
D001798:Blood Proteins; D007074:Immunoglobulin G; D040201:Platelet Membrane Glycoprotein IIb; D012333:RNA, Messenger; C069282:multimerin; D005165:Factor V; D005340:Fibrinogen