Sorting of gp80 (GPIII, clusterin), a marker protein for constitutive apical secretion in Madin-Darby canine kidney (MDCK) cells, into the regulated pathway in the pheochromocytoma cell line PC12.

We have studied the biogenesis and transport of a marker protein for constitutive apical secretion in Madin-Darby canine kidney (MDCK) cells, the gp80 glycoprotein complex (clusterin, apolipoprotein J, complement lysis inhibitor), in the rat pheochromocytoma cell line, PC12, by pulse-chase analysis of the endogeneously expressed complex. We demonstrate that in PC12 cells, gp80 is secreted via the regulated pathway, although sorting into that pathway is inefficient. Of the newly synthesized complex, 50% is released constitutively during a 2.5 h chase, 15% is released by depolarization-induced secretion, 35% stay associated with the cells. In contrast to their pivotal role in the constitutive apical exocytosis of the gp80 complex in MDCK cells, the N-linked carbohydrate moieties are dispensible for the sorting of this protein into the regulated pathway in PC12 cells, suggesting that distinct signals and sorting mechanisms are involved in these pathways.