title: Carboxypeptidase E does not mediate von Willebrand factor targeting to storage granules.
abstract: Sorting of von Willebrand factor precursor (pro-vWf) from the trans-Golgi network to secretory granules (Weibel-Palade bodies) is critical for its conversion to the biologically active highly multimeric form, as well as for regulated secretion by the endothelial cells. When expressed in hormone-secretory cells, vWf is also recognized as a stored protein and is directed to storage granules. Recently, carboxypeptidase E (CPE) was proposed as a granular sorting receptor for prohormones (Cool et al., Cell 88: 73, 1997). To explore whether CPE is also involved in pro-vWf sorting, we initially examined its expression in human umbilical vein endothelial cells. A specific message for CPE and the protein itself were detected making it a plausible candidate as a targeting receptor for vWf in endothelium. To investigate this possibility, we used mice lacking CPE. The highly multimeric forms, subunit composition and plasma levels of vWf in CPE-deficient mice were similar to those of their wild-type littermates. vWf was also found in alpha-granules of platelets and in Weibel-Palade bodies of endothelial cells obtained from the CPE-deficient mice. Furthermore, vWf was released from the cultured CPE-deficient endothelial cells after stimulation with a secretagogue. We conclude that CPE is not essential for sorting vWf to the regulated secretory pathway. Thus, a CPE-independent mechanism must exist for protein sorting to storage granules.
authors.affiliation: The Center for Blood Research and the Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: N
authors.initials: N
authors.lastname: Methia
authors.forename: C V
authors.initials: CV
authors.lastname: Denis
authors.forename: D D
authors.initials: DD
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001692:Biological Transport; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000502:physiology*; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000502:physiology* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D014162:Transfection; D014841:von Willebrand Factor / Q000502:physiology*
chemical_list: D014841:von Willebrand Factor; D002268:Carboxypeptidases; D043423:Carboxypeptidase H