Carboxypeptidase Z is present in the regulated secretory pathway and extracellular matrix in cultured cells and in human tissues

Carboxypeptidase Z (CPZ) is a newly reported member of the metallocarboxype ptidase gene family, but unlike other members of this family, CPZ contains an N-terminal domain that has amino acid sequence similarity to Wnt-binding proteins. In order to gain insights as to the potential function of CPZ, t he intracellular localization of this protein was determined in cell cultur e and in human tissues, When expressed in the AtT-20 mouse pituitary cell l ine, CPZ protein is routed to the regulated secretory pathway and secreted upon stimulation. A fraction of the secreted CPZ remains associated with th e extracellular matrix. Endogenous CPZ in the PC12 rat pheochromocytoma cel l line is also associated with the extracellular matrix. In human placenta, CPZ is present within invasive trophoblasts and in the surrounding extrace llular space, indicating an association with extracellular matrix. CPZ is a lso present in amnion cells, but is not readily apparent in the extracellul ar matrix of this cell type. A human adenocarcinoma of the colon shows expr ession of CPZ in the extracellular matrix adjacent to malignant cells. Take n together, CPZ appears to be a component of the extracellular matrix in so me cell types, where it may function in the binding of Wnt.