Carboxypeptidase E does not mediate von Willebrand factor targeting to storage granules

Sorting of von Willebrand factor precursor (pro-vWf) from the trans-Golgi n etwork to secretory granules (Weibel-Palade bodies) is critical for its con version to the biologically active highly multimeric form, as well as for r egulated secretion by the endothelial cells, When expressed in hormone-secr etory cells, vWf is also recognized as a stored protein and is directed to storage granules. Recently, carboxypeptidase E (CPE) was proposed as a gran ular sorting receptor for prohormones (Cool et al,, Cell 88: 73, 1997), To explore whether CPE is also involved in pro-vWf sorting, we initially exami ned its expression in human umbilical vein endothelial cells. A specific me ssage for CPE and the protein itself were detected making it a plausible ca ndidate 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 fro m the CPE-deficient mice. Furthermore, vWf was released from the cultured C PE-deficient endothelial cells after stimulation with a secretagogue, We co nclude 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.