Multimerin processing by cells with and without pathways for regulated protein secretion.
Multimerin is a massive, soluble, homomultimeric, factor V-binding protein found in platelet alpha-granules and in vascular endothelium. Unlike platelets, endothelial cells contain multimerin within granules that lack the secretory granule membrane protein P-selectin, and in culture, they constitutively secrete most of their synthesized multimerin. To further evaluate multimerin's posttranslational processing and storage, we expressed human endothelial cell prepromultimerin in a variety of cell lines, with and without pathways for regulated secretion. The recombinant multimerin produced by these different cells showed variations in its glycosylation, proteolytic processing, and multimer profile, and human embryonic kidney 293 cells recapitulated multimerin's normal processing for constitutive secretion by human endothelial cells. When multimerin was expressed in a neuroendocrine cell line capable of regulated protein secretion, it was efficiently targeted for regulated secretion. However, the multimerin stored in these cells was proteolyzed more extensively than normally occurs in platelets, suggesting that endoproteases similar to those expressed by megakaryocytes are required to produce platelet-type multimerin. The impact of the tissue-specific differences in multimerin's posttranslational processing on its functions is not yet known. Multimerin's sorting and targeting for regulated secretion may be important for its functions and its association with factor V in secretion granules.
Hayward
C P
CP
Departments of Pathology and Molecular Medicine, Laboratory Medicine, and Medicine, McMaster University, Hamilton, Ontario, Canada.
Song
Z
Z
Zheng
S
S
Fung
R
R
Pai
M
M
Massé
J M
JM
Cramer
E M
EM
D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D001798:Blood Proteins / Q000378:metabolism*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D016253:Microscopy, Immunoelectron; D009928:Organ Specificity; D011499:Protein Processing, Post-Translational
D001798:Blood Proteins; C069282:multimerin