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 platel ets, endothelial cells contain multimerin within granules that lack the sec retory granule membrane protein P-selectin, and in culture, they constituti vely secrete most of their synthesized multimerin. To further evaluate mult imerin's posttranslational processing and storage, we expressed human endot helial cell prepromultimerin in a variety of cell lines, with and without p athways for regulated secretion. The recombinant multimerin produced by the se different cells showed variations in its glycosylation, proteolytic proc essing, and multimer profile, and human embryonic kidney 293 cells recapitu lated multimerin's normal processing for constitutive secretion by human en dothelial cells. When multimerin was expressed in a neuroendocrine cell lin e capable of regulated protein secretion, it was efficiently targeted for r egulated secretion, However, the multimerin stored in these cells was prote olyzed 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 differe nces in multimerin's posttranslational processing on its functions is not y et known, Multimerin's sorting and targeting for regulated secretion may be important for its functions and its association with factor V in secretion granules. (C) 1999 by The American Society of Hematology.